TERE1/UBIAD1抑制膀胱癌的分子机制研究及TERE1/UBIAD1的结构与功能分析
|
摘要
目的检测分析临床膀胱癌组织和正常膀胱组织TERE1/UBIAD1表达及Ras-MAPK信号通路的变化。
方法采用免疫组化检测分析人正常膀胱组织及膀胱癌组织中TERE1和端粒逆转录酶(hTERT)的蛋白表达水平：用RT-PCR及western blotting检测膀胱癌组织中TERE1和hTERT的表达水平及Ras-MAPK信号通路关键分子的变化。
结果1.免疫组化结果表明相对于正常膀胱组织,膀胱癌组织中TERE1染色明显减低。按组织学分级G3-4期TERE1染色阳性率为16.13%(5／31例数),与G2期阳性率TERE1为51.85%(14／27)相比具有显著性差异,与G1期阳性率为76.00%(19／25)相比差异具有极显著性；膀胱癌按临床分期T2期TERE1染色阳性率为27.27%(6／22),T3-4期TERE1染色阳性率为16.00%(4／25),与Ta期94.12%(16／17)和T1期阳性率为68.42%(13／19)相比,具有显著性差异。2.膀胱癌组织中TERE1的mRNA和蛋白表达水平与正常膀胱组织相比明显下降(P<0.05)。3.癌组织中hTERT的mRNA和蛋白表达与正常膀胱组织相比明显上升(P<0.05)。4.膀胱癌组织中磷酸化ERK、磷酸化MEK(1／2)、磷酸化B-Raf(Ser455)及磷酸化C-Raf(Ser338)蛋白表达水平与正常组织相比明显增加(P<0.05),而膀胱癌组织与正常膀胱组织中总的ERK、MEK(1/2)、A-Raf、B-Raf, C-Raf及磷酸化A-Raf (Ser299)蛋白表达没有明显差异。
结论膀胱癌中TERE1/UBIAD1表达较正常组织明显下调,且与膀胱癌分级分期密切相关,高恶性度肿瘤未能检测到TERE1/UBIAD1的表达。膀胱癌中Ras-MAPK信号通路关键分子较正常组织相比明显被激活；hTERT表达增加。TERE1/UBIAD1可能通过Ras-MAPK信号通路激活影响膀胱癌的形成。
第二部分TERE1／UBIAD1抑制膀胱癌的分子机制研究
目的研究TERE1/UBIAD1抑制膀胱癌的作用机制是否通过Ras-MAPK信号通路及作用的分子靶点。
方法1.采用RT-PCR及western blotting检测膀胱癌细胞系T24中TERE1和hTERT的mRNA和蛋白表达水平及Ras-MAPK信号通路中关键分子的变化。2. siRNA干扰技术实验：分阴性对照组、转染试剂对照组、TERE1-291-siRNA组、TERE1-322-siRNA组、TERE1-396-siRNA组,将化学修饰的TERE1-siRNA oligos转染L02正常细胞系48小时后,用RT-PCR及western blotting检测TERE1和hTERT的mRNA及蛋白表达水平,western blotting分析Ras-MAPK信号通路关键分子的变化,用细胞计数和MTT法检测细胞增殖情况。3.MEK抑制剂U0126实验：分阴性对照组、TERE1-291-siRNA组、TERE1-322-siRNA组,将化学修饰的TERE1-siRNA oligos转染L02正常细胞系48小时后再加入MEK抑制剂U0126作用30分钟,western blotting检测Ras-MAPK信号通路关键分子的变化。
结果1.膀胱癌细胞系T24与正常细胞系L02比较,TERE1的mRNA及蛋白表达水平明显下调,Ras-MAPK信号通路分子磷酸化的ERK表达明显上升；hTERT的mRNA及蛋白表达增加。2.与阴性对照组或转染试剂组相对比,化学修饰的TERE1-291-siRNA oligos和TERE1-322-siRNA oligos转染正常细胞48小时后能明显将细胞TERE1基因沉默,使hTERT的mRNA和蛋白表达水平上升(P<0.05),磷酸化的ERK蛋白表达水平显著增加(P<0.01),同时细胞数目增多、细胞增殖加快。3.TERE1-291-siRNA和TERE1-322-siRNA作用组,加抑制剂U0126与不加抑制剂U0126相比,Ras-MAPK信号途径中关键分子ERK的蛋白磷酸化被抑制,hTERT的蛋白表达被部分抑制。
结论TERE1基因沉默能激活细胞Ras-MAPK信号通路及导致细胞增殖明显加快,MEK抑制剂能阻滞TERE1下调引起的Ras-MAPK信号通路的激活,部分阻滞hTERT蛋白表达。TERE1可能作为Ras-MAPK信号通路的负向调节因子,在膀胱癌的发生中有重要作用。
Part 1 Analysis of TERE1/UBIAD1 expression and Ras-MAPK signalling pathway in bladder cancer
Objective Detection of TERE1 (transitional epithelial response gene)/UBIAD1(UbiA prenyltransferase domain containing 1) expression and Ras-MAPK signal pathway molecules changes in clinical bladder cancer tissues and normal bladder tissues.
Methods Analysis of TERE1 and human telomerase reverse transcriptase (hTERT) protein expression in normal bladder tissue and bladder cancer tissues using immunohistochemistry; the expression of TERE1、hTERT in bladder cancer tissues and normal bladder tissues and the Ras-MAPK signaling pathway molecules changes were determined by RT-PCR and western blotting.
Results 1. Immunohistochemistry results showed that compared with normal bladder tissue, TERE1 staining in bladder cancer tissues were reduced. According to histological grade, the positive rate 16.13%(5/31 the number of cases) on G3-4 TERE1 staining was different compared with 51.85%(14/27) on grade G2, the positive rate 16.13%on G3-4 TERE1 staining was significant difference compared to the positive rate 76.00%(19/25) on grade G1; according to clinical bladder cancer stage, the positive rate of TERE1 was 27.27%(6/22) in T2 stage, TERE1 positive staining rate was 16.00%(4/25) in T3-4 stage,68.42%(13/19) in T1 stage and 94.12%(16/17) in Ta stage.2. The mRNA and protein expression levels of TERE1 in bladder cancer tissues were decreased significantly compared with normal bladder tissues (P<0.05).3. The mRNA and protein expressions of hTERT in bladder carcinoma significantly increased.4. Compared with normal tissue, phosphorylated protein levels of ERK、MEK(1/2)、B-Raf (Ser455) and C-Raf (Ser338) in bladder cancer significantly increased (P<0.05), total protein levels of ERK、MEK (1/ 2)、A-Raf, B-Raf, C-Raf and phosphorylated protein levels of A-Raf (Ser299) in bladder cancer tissues and normal bladder tissues were no significant difference.
Conclusion TERE1/UBIAD1 expression in bladder cancer tissues was significantly lower than normal tissues, TERE1/UBIAD1 expression was closely related with the grade and stage of bladder cancer. The expression of TERE1/UBIAD1 was no detected in high grade tumors. Ras-MAPK signaling pathway molecules in bladder cancer were significantly activated compared to normal bladder tissues; The hTERT expression in bladder cancer was significantly increased. TERE1/UBIAD1 possibly affected the formation of bladder cancer through activated Ras-MAPK signaling pathway.
Part 2 Molecular mechanism of the role of TERE1/UBIAD1 in bladder cancer suppression
Objective To study the molecular mechanism of the inhibition role of TERE1/UBI ADI in bladder cancer through the Ras-MAPK signaling pathway and the molecular targets in Ras-MAPK signaling pathway.
Methods 1. The mRNA and protein expression levels of TERE1 and hTERT in bladder cancer cell line T24 were determined by RT-PCR and western blotting, the Ras-MAPK signaling pathway was also detected using western blotting.2. SiRNA interference experiments:experiments were divided into negative control group、the transfection reagent control group、TERE1-291-siRNA group、TERE1-322-siRNA group、TERE1-396-siRNA group, the chemical modification of TERE1-siRNA oligos transfected L02 normal cells for 48 hours, the mRNA and protein levels of TERE1 and hTERT were measured by RT-PCR and western blotting, the Ras-MAPK signaling pathway molecules were analyzed by western blotting, cell proliferation assay were determined using cell technology and MTT assay.3. MEK inhibitor U0126 tests:experiments were divided into negative control group、TERE 1-291-siRNA group、TERE1-322-siRNA group, the chemical modification of TERE1-siRNA oligos normal L02 cells transfected for 48 hours, then pretreated adding MEK inhibitor U0126 for 30 minutes, the Ras-MAPK signaling pathway molecules changes were detected using western blotting.
Results 1. The mRNA and protein levels of TERE1 in T24 bladder cancer cell line were significantly reduced compared with the normal cell line L02, the phosphorylation protein levels of ERK in Ras-MAPK signaling pathway was significantly increased; mRNA and protein expression of hTERT were also increased.2. Compared to the negative group or the transfection reagent group, TERE1 gene in normal cells was significantly silenced by chemical modification of TERE1-291-siRNA oligos and TERE1-322-siRNA oligos, the mRNA and protein levels of hTERT were increased (P<0.05), phosphorylated ERK protein levels was increased significantly (P<0.01), while cell number were increased andcell proliferation was accelerated.3. Adding inhibitor U0126, the ERK protein phosphorylation levels was inhibited in TERE1-291-siRNA group and TERE1-322-siRNA group compared to without inhibitor U0126, the protein expression of hTERT was partially inhibited.
Conclusions TERE1 gene silencing can activate Ras-MAPK signaling pathway and lead to cell proliferation, MEK inhibitor can suppress the activation of Ras-MAPK signaling pathway due to down-regulation of TERE1, partially block the expression of hTERT protein. TERE1 might serve as a negative regulator Ras-MAPK signaling pathway and might have an important role in bladder carcinogenesis.
方法采用免疫组化检测分析人正常膀胱组织及膀胱癌组织中TERE1和端粒逆转录酶(hTERT)的蛋白表达水平：用RT-PCR及western blotting检测膀胱癌组织中TERE1和hTERT的表达水平及Ras-MAPK信号通路关键分子的变化。
结果1.免疫组化结果表明相对于正常膀胱组织,膀胱癌组织中TERE1染色明显减低。按组织学分级G3-4期TERE1染色阳性率为16.13%(5／31例数),与G2期阳性率TERE1为51.85%(14／27)相比具有显著性差异,与G1期阳性率为76.00%(19／25)相比差异具有极显著性；膀胱癌按临床分期T2期TERE1染色阳性率为27.27%(6／22),T3-4期TERE1染色阳性率为16.00%(4／25),与Ta期94.12%(16／17)和T1期阳性率为68.42%(13／19)相比,具有显著性差异。2.膀胱癌组织中TERE1的mRNA和蛋白表达水平与正常膀胱组织相比明显下降(P<0.05)。3.癌组织中hTERT的mRNA和蛋白表达与正常膀胱组织相比明显上升(P<0.05)。4.膀胱癌组织中磷酸化ERK、磷酸化MEK(1／2)、磷酸化B-Raf(Ser455)及磷酸化C-Raf(Ser338)蛋白表达水平与正常组织相比明显增加(P<0.05),而膀胱癌组织与正常膀胱组织中总的ERK、MEK(1/2)、A-Raf、B-Raf, C-Raf及磷酸化A-Raf (Ser299)蛋白表达没有明显差异。
结论膀胱癌中TERE1/UBIAD1表达较正常组织明显下调,且与膀胱癌分级分期密切相关,高恶性度肿瘤未能检测到TERE1/UBIAD1的表达。膀胱癌中Ras-MAPK信号通路关键分子较正常组织相比明显被激活；hTERT表达增加。TERE1/UBIAD1可能通过Ras-MAPK信号通路激活影响膀胱癌的形成。
第二部分TERE1／UBIAD1抑制膀胱癌的分子机制研究
目的研究TERE1/UBIAD1抑制膀胱癌的作用机制是否通过Ras-MAPK信号通路及作用的分子靶点。
方法1.采用RT-PCR及western blotting检测膀胱癌细胞系T24中TERE1和hTERT的mRNA和蛋白表达水平及Ras-MAPK信号通路中关键分子的变化。2. siRNA干扰技术实验：分阴性对照组、转染试剂对照组、TERE1-291-siRNA组、TERE1-322-siRNA组、TERE1-396-siRNA组,将化学修饰的TERE1-siRNA oligos转染L02正常细胞系48小时后,用RT-PCR及western blotting检测TERE1和hTERT的mRNA及蛋白表达水平,western blotting分析Ras-MAPK信号通路关键分子的变化,用细胞计数和MTT法检测细胞增殖情况。3.MEK抑制剂U0126实验：分阴性对照组、TERE1-291-siRNA组、TERE1-322-siRNA组,将化学修饰的TERE1-siRNA oligos转染L02正常细胞系48小时后再加入MEK抑制剂U0126作用30分钟,western blotting检测Ras-MAPK信号通路关键分子的变化。
结果1.膀胱癌细胞系T24与正常细胞系L02比较,TERE1的mRNA及蛋白表达水平明显下调,Ras-MAPK信号通路分子磷酸化的ERK表达明显上升；hTERT的mRNA及蛋白表达增加。2.与阴性对照组或转染试剂组相对比,化学修饰的TERE1-291-siRNA oligos和TERE1-322-siRNA oligos转染正常细胞48小时后能明显将细胞TERE1基因沉默,使hTERT的mRNA和蛋白表达水平上升(P<0.05),磷酸化的ERK蛋白表达水平显著增加(P<0.01),同时细胞数目增多、细胞增殖加快。3.TERE1-291-siRNA和TERE1-322-siRNA作用组,加抑制剂U0126与不加抑制剂U0126相比,Ras-MAPK信号途径中关键分子ERK的蛋白磷酸化被抑制,hTERT的蛋白表达被部分抑制。
结论TERE1基因沉默能激活细胞Ras-MAPK信号通路及导致细胞增殖明显加快,MEK抑制剂能阻滞TERE1下调引起的Ras-MAPK信号通路的激活,部分阻滞hTERT蛋白表达。TERE1可能作为Ras-MAPK信号通路的负向调节因子,在膀胱癌的发生中有重要作用。
Part 1 Analysis of TERE1/UBIAD1 expression and Ras-MAPK signalling pathway in bladder cancer
Objective Detection of TERE1 (transitional epithelial response gene)/UBIAD1(UbiA prenyltransferase domain containing 1) expression and Ras-MAPK signal pathway molecules changes in clinical bladder cancer tissues and normal bladder tissues.
Methods Analysis of TERE1 and human telomerase reverse transcriptase (hTERT) protein expression in normal bladder tissue and bladder cancer tissues using immunohistochemistry; the expression of TERE1、hTERT in bladder cancer tissues and normal bladder tissues and the Ras-MAPK signaling pathway molecules changes were determined by RT-PCR and western blotting.
Results 1. Immunohistochemistry results showed that compared with normal bladder tissue, TERE1 staining in bladder cancer tissues were reduced. According to histological grade, the positive rate 16.13%(5/31 the number of cases) on G3-4 TERE1 staining was different compared with 51.85%(14/27) on grade G2, the positive rate 16.13%on G3-4 TERE1 staining was significant difference compared to the positive rate 76.00%(19/25) on grade G1; according to clinical bladder cancer stage, the positive rate of TERE1 was 27.27%(6/22) in T2 stage, TERE1 positive staining rate was 16.00%(4/25) in T3-4 stage,68.42%(13/19) in T1 stage and 94.12%(16/17) in Ta stage.2. The mRNA and protein expression levels of TERE1 in bladder cancer tissues were decreased significantly compared with normal bladder tissues (P<0.05).3. The mRNA and protein expressions of hTERT in bladder carcinoma significantly increased.4. Compared with normal tissue, phosphorylated protein levels of ERK、MEK(1/2)、B-Raf (Ser455) and C-Raf (Ser338) in bladder cancer significantly increased (P<0.05), total protein levels of ERK、MEK (1/ 2)、A-Raf, B-Raf, C-Raf and phosphorylated protein levels of A-Raf (Ser299) in bladder cancer tissues and normal bladder tissues were no significant difference.
Conclusion TERE1/UBIAD1 expression in bladder cancer tissues was significantly lower than normal tissues, TERE1/UBIAD1 expression was closely related with the grade and stage of bladder cancer. The expression of TERE1/UBIAD1 was no detected in high grade tumors. Ras-MAPK signaling pathway molecules in bladder cancer were significantly activated compared to normal bladder tissues; The hTERT expression in bladder cancer was significantly increased. TERE1/UBIAD1 possibly affected the formation of bladder cancer through activated Ras-MAPK signaling pathway.
Part 2 Molecular mechanism of the role of TERE1/UBIAD1 in bladder cancer suppression
Objective To study the molecular mechanism of the inhibition role of TERE1/UBI ADI in bladder cancer through the Ras-MAPK signaling pathway and the molecular targets in Ras-MAPK signaling pathway.
Methods 1. The mRNA and protein expression levels of TERE1 and hTERT in bladder cancer cell line T24 were determined by RT-PCR and western blotting, the Ras-MAPK signaling pathway was also detected using western blotting.2. SiRNA interference experiments:experiments were divided into negative control group、the transfection reagent control group、TERE1-291-siRNA group、TERE1-322-siRNA group、TERE1-396-siRNA group, the chemical modification of TERE1-siRNA oligos transfected L02 normal cells for 48 hours, the mRNA and protein levels of TERE1 and hTERT were measured by RT-PCR and western blotting, the Ras-MAPK signaling pathway molecules were analyzed by western blotting, cell proliferation assay were determined using cell technology and MTT assay.3. MEK inhibitor U0126 tests:experiments were divided into negative control group、TERE 1-291-siRNA group、TERE1-322-siRNA group, the chemical modification of TERE1-siRNA oligos normal L02 cells transfected for 48 hours, then pretreated adding MEK inhibitor U0126 for 30 minutes, the Ras-MAPK signaling pathway molecules changes were detected using western blotting.
Results 1. The mRNA and protein levels of TERE1 in T24 bladder cancer cell line were significantly reduced compared with the normal cell line L02, the phosphorylation protein levels of ERK in Ras-MAPK signaling pathway was significantly increased; mRNA and protein expression of hTERT were also increased.2. Compared to the negative group or the transfection reagent group, TERE1 gene in normal cells was significantly silenced by chemical modification of TERE1-291-siRNA oligos and TERE1-322-siRNA oligos, the mRNA and protein levels of hTERT were increased (P<0.05), phosphorylated ERK protein levels was increased significantly (P<0.01), while cell number were increased andcell proliferation was accelerated.3. Adding inhibitor U0126, the ERK protein phosphorylation levels was inhibited in TERE1-291-siRNA group and TERE1-322-siRNA group compared to without inhibitor U0126, the protein expression of hTERT was partially inhibited.
Conclusions TERE1 gene silencing can activate Ras-MAPK signaling pathway and lead to cell proliferation, MEK inhibitor can suppress the activation of Ras-MAPK signaling pathway due to down-regulation of TERE1, partially block the expression of hTERT protein. TERE1 might serve as a negative regulator Ras-MAPK signaling pathway and might have an important role in bladder carcinogenesis.
引文
[1]Jemal Ahmedin, Siegel Rebecca, Ward Elizabeth, Hao Yongping, Xu Jiaquan, Thun Michael J. Cancer statistics,2009. CA Cancer J Clin.,59,225-249 (2009).
[2]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002. CA Cancer J. Clin.,55,74-108(2005).
[3]Mitral Anirban P. Cote Richard J. Molecular Pathogenesis and Diagnostics of
Bladder Cancer. Annu. Rev. Pathol. Mech. Dis..4:251-285 (2009).
[4]Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet, 374(9685):239-249 (2009).
[5]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[6]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10 (2007).
[7]Hong, L. and Rubin, G. M. "L(2)35Fc, a novel transmembrane protein required for suppression of melanotic tumors".39th Annual Drosophila Research Conference, March 25 to 29, Washington, DC. Page 128 (1998).
[8]McGravey, T.W., Nguyaen, T., and Malkowicz S.B. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J. cell. Biochem.,95,419-428 (2005).
[9]Panagiotis A, Konstantinopoulos,Michalia V,Karamouzis & Athanasios QPapavassiliou. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nature Reviews Drug Discovery, 6,541-555 (2007).
[1]Jemal Ahmedin, Siegel Rebecca, Ward Elizabeth, Hao Yongping, Xu Jiaquan, Thun Michael J. Cancer statistics,2009. CA Cancer J Clin.,59,225-249 (2009).
[2]Volanis D, Kadiyska T, Galanis A, Delakas D, Logotheti S, Zoumpourlis V. Environmental factors and genetic susceptibility promote urinary bladder cancer. Toxicol Lett.193(2):131-137 (2010).
[3]Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet,374(9685):239-249 (2009).
[4]Hartman M, Loy EY, Ku CS, Chia KS. Molecular epidemiology and its current clinical use in cancer management. Lancet Oncol.;11(4):383-390 (2010).
[5]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[6]McGravey, T.W., Nguyaen, T., Puthiyaveettil, R., Tomaszewski, J.E., and Malkowicz S.B. TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate,54,144-155(2003).
[7]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10(2007).
[8]Yellore VS, Khan MA, Bourla N, Rayner SA, Chen MC, Sonmez B, Momi RS, Sampat KM, Gorin MB, Aldave AJ. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol.Vis.,13,1777-1782 (2007).
[9]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, Lisch W, Henn W, Denninger E, Krause M, Wasson P, Ebenezer N, Mahurkar S, Nickerson ML. Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci.,48(11),5007-5012 (2007).
[10]Hong, L. and Rubin, G. M. "L(2)35Fc, a novel transmembrane protein required for suppression of melanotic tumors".39th Annual Drosophila Research Conference, March 25 to 29, Washington, DC. Page 128 (1998).
[11]Hong Ling, Xia, Y, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Hubei Genetics Meeting VIII, November 2009, Wuhan, Hubei, P.R.China page 140 (2009).
[12]Hong Ling, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Genetics Society of model organisms and human health seminar of China, Nanchang, Jiangxi, April 2010, Nanchang, P.R.China page 38 (2010).
[13]Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR. Telomerase catalytic subunit homologs from fission yeast and human. Science,277(5328),955-959 (1997).
[14]Hiyama E, Hiyama K. Telomerase as tumor marker. Cancer Lett.194(2):221-33 (2003).
[15]Kyo S, Inoue M. Complex regulatory mechanisms of telomerase activity in normal and cancer cells:how can we apply them for cancer therapy? Oncogene. 21(4):688-697(2002).
[16]Kyo S, Takakura M, Fujiwara T, Inoue M. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci.,99(8), 1528-1538(2008).
[17]Maida Y, Kyo S, Kanaya T, Wang Z, Yatabe N, Tanaka M, Nakamura M, Ohmichi M, Gotoh N,, Murakami S, Inoue M. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Oncogene, 21(26),4071-4079 (2002).
[18]Dwyer J, Li H, Xu D, Liu JP. Transcriptional regulation of telomerase activity:roles of the the Ets transcription factor family. Ann N Y Acad Sci. Oct;1114:36-47 (2007).
[19]Mitral Anirban P. Cote Richard J. Molecular Pathogenesis and Diagnostics of Bladder Cancer. Annu. Rev. Pathol. Mech. Dis.4:251-285 (2009).
[20]Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 100:57-70 (2000).
[21]Langzam L, Koren R, Gal R, Kugel V, Paz A, et al. Patterns of protein kinase C isoenzyme expression in transitional cell carcinoma of bladder:relation to degree of malignancy. Am. J. Clin. Pathol.116:377-85 (2001).
[22]Varga A, Czifra G, Tallai B, Nemeth T, Kovacs I, et al. Tumor grade-dependent alterations in the protein kinase C isoform pattern in urinary bladder carcinomas. Eur. Urol.46:462-65 (2004).
[23]Wu X, Obata T, Khan Q, Highshaw RA, De Vere White R, Sweeney C. The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion. Br. J. Urol.Int.93:143-50 (2001).
[24]Nakanishi C, Toi M. Nuclear factor-κB inhibitors as sensitizers to anticancer drugs. Nat. Rev. Cancer 5:297-309 (2005).
[25]Jebar AH, Hurst CD, Tomlinson DC, Johnston C, Taylor CF, Knowles MA. FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 24:5218-5225 (2005).
[26]Mitra AP, Lin H, Datar RH, Cote RJ. Molecular biology of bladder cancer:prognostic and clinical implications. Clin. Genitourin. Cancer 5:67-77 (2006).
[27]Kramer C, Klasmeyer K, Bojar H, Schulz WA, Ackermann R, Grimm MO. Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB 1 expression in bladder cancer and their relation to clinical outcome. Cancer 109:2016-24 (2007).
[28]Memon AA, Sorensen BS, Meldgaard P, Fokdal L, Thykjaer T, Nexo E. The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4:a study in bladder cancer patients. Br. J. Cancer 94:1703-9 (2006).
[29]A.P. Mitra, R.H. Datar and R.J. Cote, Molecular pathways in invasive bladder cancer: New insights into mechanisms, progression, and target identification, J Clin Oncol 24. 5552-5564 (2006).
[30]Knowles MA. Molecular subtypes of bladder cancer:Jekyll and Hyde or chalk and cheese? Carcinogenesis.27:361-73 (2006).
[31]Hu, M., and Polyak, K. Microenvironmental regulation of cancer development. Curr. Opin. Genet. Dev.18,27-34 (2008).
[32]Yang Jing, Chun Liu, Junmin Xu, Liya WangA. Novel UBIAD1 mutation identified in a Chinese family with Schnder crystalline corneal dystrophy. Molecular Vision.1463-1469(2009).
[33]Nagai H, Negrini M, Carter SL, Gillum DR, Rosenberg AL, Schwartz GF and Croce CM. Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer. Cancer Res.,55,1752-1757 (1995).
[34]Praml C, Finke LH, Herfarth C, Schlag P, Schwab M and Amler L. Deletion mapping defines different regions in 1p34.2-pter that may harbor genetic information related to human colorectal cancer. Oncogene,11,1357-1362 (1995).
[35]Bieche I, Khodja A, Lidereau R. Deletion mapping in breast tumor cell lines points to two distinct tumor-suppressor genes in the 1p32-pter region, one of deleted regions (1p36.2) being located within the consensus region of LOH in neuroblastoma. Oncol Rep.5(1):267-72 (1998).
[36]Hogarty MD, Maris JM, White PS, Guo C, Brodeur GM. Analysis of genomic imprinting at 1p35-36 in neuroblastoma. Med Pediatr Oncol.36(1):52-55 (2001).
[37]Ebrahimi SA, Wang EH, Wu A, Schreck RR, Passaro Jr E and Sawicki MP. Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors. Cancer Res.,59, 311-315(1999).
[38]Jiang H, Orr A, Guernsey DL, Robitaille J, Asselin G, Samuels ME, Dube MP. Application of homozygosity haplotype analysis to genetic mapping with high-density SNP genotype data. PLoS One.4(4):e5280 (2009).
[39]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, Lisch W, Dupps WJ Jr, White PS, Winters RS, Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu da W, Ebenezer N, Nickerson ML. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A.146(3):271-283 (2008).
[40]Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011-2015 (1994).
[41]Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell.97:527-538 (1999).
[42]Dwyer JM, Liu JP. Ets2 transcription factor, telomerase activity and breast cancer. Clin Exp Pharmacol Physiol.37(1):83-87 (2010).
[43]Panagiotis A, Konstantinopoulos, Michalia V, Karamouzis & Athanasios G, Papavassiliou. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nature Reviews Drug Discovery 6,541-555 (2007).
[44]Oldham, W. M., Van Eps, N., Preininger, A. M., Hubbell, W. L.& Hamm, H. E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nature Struct. Mol. Biol.9,772-777 (2006).
[45]Michael H Gelb,Lucas Brunsveld,Christine A Hrycyna,Susan Michaelis,Fuyuhiko Tamanoi,Wesley C Van Voorhis&Herbert Waldmann. Therapeutic intervention based on protein prenylation and associated modifications. Nature Chemical Biology. 2,518-528(2006).
[46]U.R. Rapp, M.D. Goldsborough, G.E. Mark, T.I. Bonner, J. Groffen, F.H. Reynolds Jr., J.R. Stephenson, Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus, Proc. Natl. Acad. Sci. U. S. A.804218-4222 (1983).
[47]T. Bonner, S.J. O'Brien, W.G. Nash, U.R. Rapp, C.C. Morton, P. Leder,The human homologs of the raf (mil) oncogene are located on human chromosomes 3 and 4, Science.223,71-74(1984).
[48]C. Hagemann, U.R. Rapp, Isotype-specific functions of Raf kinases, Exp.Cell Res.253, 34-46(1999).
[49]C. Wellbrock, M. Karasarides, R. Marais, The RAF proteins take centre stage, Nat. Rev., Mol. Cell Biol.5,875-885 (2004).
[50]K. Mercer, S. Giblett, A. Oakden, J. Brown, R. Marais, C. Pritchard,A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression, Oncogene 24,5207-5217 (2005).
[51]Y.H. Hwang, J.Y. Choi, S. Kim, E.S. Chung, T. Kim, S.S. Koh, B. Lee,S.H. Bae, J. Kim, Y.M. Park, Over-expression of c-raf-1 protooncogene in liver cirrhosis and hepatocellular carcinoma, Hepatol. Res.29,113-121(2004).
[52]R. Mukherjee, J.M. Bartlett, N.S. Krishna, M.A. Underwood, J. Edwards, Raf-1 expression may influence progression to androgen insensitive prostate cancer, Prostate 64,101-107 (2005).
[53]S. Wang, R.N. Ghosh, S.P. Chellappan, Raf-1 physically interacts with Rb and regulates its function:a link between mitogenic signaling and cell cycle regulation, Mol. Cell. Biol.18,7487-7498 (1998).
[54]E.T. Keller, Z. Fu, M. Brennan, The biology of a prostate cancer metastasis suppressor protein:Raf kinase inhibitor protein, J. Cell. Biochem.94,273-278 (2005).
[55]V. Emuss, M. Garnett, C. Mason, R. Marais, Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF, Cancer Res.65,9719-9726 (2005).
[56]Karreth FA, DeNicola GM, Winter SP, Tuveson DA. C-Raf inhibits MAPK activation and transformation by B-Raf (V600E). Mol Cell.36(3):477-486(2009).
[1]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[2]McGravey, T.W., Nguyaen, T., Puthiyaveettil, R., Tomaszewski, J.E., and Malkowicz S.B. TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate,54,144-155 (2003).
[3]Hong, L. and Rubin, G. M. "L(2)35Fc, a novel transmembrane protein required for suppression of melanotic tumors".39th Annual Drosophila Research Conference, March 25 to 29, Washington, DC. Page 128 (1998).
[4]Xia, Y and Hong Ling, "TERE1/UBIAD1, a bridge between lipid metabolism and carcinogenesis", International Symposium on Lipid and Tissue Injury Nov26-29 2009, ChongQing,China page 75 (2009).
[5]Hong Ling, Xia, Y, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Hubei Genetics Meeting Ⅷ, November 2009, Wuhan, Hubei, P.R.China page 140 (2009).
[6]Hong Ling, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Genetics Society of model organisms and human health seminar of China, Nanchang, Jiangxi, April 2010, Nanchang, P.R.China page 38 (2010).
[7]Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet,374(9685):239-249 (2009).
[8]Wu XR. Urothelial tumorigenesis:a tale of divergent pathways. Nat. Rev. Cancer. 5:713-25 (2005).
[9]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, Lisch W, Henn W, Denninger E, Krause M, Wasson P, Ebenezer N, Mahurkar S, Nickerson ML Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci.,48(11),5007-5012 (2007).
[10]Yellore VS, Khan MA, BourlaN, Rayner SA, Chen MC, Sonmez B, Momi RS, Sampat KM, Gorin MB, Aldave AJ. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol. Vis.,13,1777-1782 (2007).
[11]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, Lisch W, Dupps WJ Jr, White PS, Winters RS, Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu da W, Ebenezer N, Nickerson ML. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A.146(3):271-283 (2008).
[12]McGravey, T.W., Nguyaen, T., and Malkowicz S.B. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J. cell. Biochem.,95,419-428 (2005).
[13]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10(2007).
[14]Zhang, F. L.& Casey, P. J. Protein prenylation:molecular mechanisms and functional consequences. Annu. Rev. Biochem.65,241-269 (1996).
[15]Winter-Vann, A. M.& Casey, P. J. Post-prenylationprocessing enzymes as new targets in oncogenesis. Nature Rev. Cancer.5,405-412 (2005).
[16]Oldham, W. M., Van Eps, N., Preininger, A. M., Hubbell, W. L.& Hamm, H. E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nature Struct. Mol. Biol.9,772-777. (2006).
[17]Pfeffer, S.& Aivazian, D. Targeting Rab GTPases to distinct membrane compartments. Nature Rev. Mol. Cell Biol.5,886-896 (2004).
[18]Doll, R. J., Kirschmeier, P.& Bishop, W. R. Farnesyltransferase inhibitors as anticancer agents:critical crossroads. Curr. Opin. Drug Discov. Devel.7,478-486 (2004).
[19]Sebti, S. M.& Der, C. J. Searching for the elusive targets of farnesyltransferase inhibitors. Nature Rev. Cancer 3,945-951 (2003).
[20]Knowles MA. What we could do now:molecular pathology of bladder cancer. Mol. Pathol.54:215-221 (2001).
[21]Mitra AP, Cote RJ. Searching for novel therapeutics and targets:insights from clinical trials. Urol. Oncol.25:341-343 (2007).
[22]Mitral Anirban P. Cote Richard J. Molecular Pathogenesis and Diagnostics of Bladder Cancer. Annu. Rev. Pathol. Mech. Dis.4:251-285 (2009).
[23]Hanahan D,Weinberg RA. The hallmarks of cancer. Cell 100:57-70 (2000).
[24]Mitra AP, Lin H, Datar RH, Cote RJ. Molecular biology of bladder cancer:prognostic and clinical implications. Clin. Genitourin. Cancer 5:67-77 (2006).
[25]Lopez-Knowles E, Hernandez S, Kogevinas M, Lloreta J, Amoros A, Tardon A, Carrato A, Kishore S, Serra C, Malats N, Real FX; EPICURO Study Investigators. The p53 pathway and outcome among patients with T1G3 bladder tumors. Clin Cancer Res. 12(20 Pt 1):6029-6036 (2006).
[26]Liukkonen T, Rajala P, Raitanen M, Rintala E, Kaasinen E, Lipponen P. Prognostic value of MIB-1 score, p53, EGFr, mitotic index and papillary status in primary superficial (Stage pTa/T1) bladder cancer:a prospective comparative study. Eur. Urol. 36:393-400(1999).
[27]Chatterjee SJ, Datar R, Youssefzadeh D, George B, Goebell PJ, Stein JP, Young L, Shi SR, Gee C, Groshen S, Skinner DG, Cote RJ. Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma, J Clin Oncol 22. 1007-1013 (2004).
[28]Shariat SF, Youssef RF, Gupta A, Chade DC, Karakiewicz PI, Isbarn H, Jeldres C, Sagalowsky AI, Ashfaq R, Lotan Y. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol.183(5):1744-1750 (2010).
[29]Birkhahn M, Mitra AP, Cote RJ. Molecular markers for bladder cancer:the road to a multimarker approach. Expert Rev. Anticancer Ther. 7:1717-1727 (2007).
[30]Wolf HK, Stober C, Hohenfellner R, Leissner J. Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumor Biol.22:328-336 (2001).
[31]Maluf FC, Cordon-Cardo C, Verbel DA, Satagopan JM, Boyle MG, et al. Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment. Ann. Oncol.17:1677-86(2006).
[32]Gabriel U, Bolenz C, Becker A, Schaaf A, Steidler A, Trojan L, Weiss C, Michel MS. Evaluation of cytotoxic effects induced by bcl-2 and bcl-xL antisense-oligodeoxynucleotides in normal urothelium and transitional cell carcinoma. Oncol Rep.20(6):1419-1423 (2008).
[33]Soung YH, Lee JW, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH. BH3 domain mutation of proapoptotic genes Bad, Bmf and Bcl-G is rare in transitional cell carcinomas of the urinary bladder. Pathology 38:33-34 (2006).
[34]Chen FH, Crist SA, Zhang GJ, Iwamoto Y, See WA. Interleukin-6 production by human bladder tumor cell lines is up-regulated by bacillus Calmette-Guerin through nuclear factor-KB and Ap-1 via an immediate early pathway. J. Urol.168:786-97 (2002).
[35]Hess J, Angel P, Schorpp-Kistner M.2004. AP-1 subunits:quarrel and harmony among siblings.J. Cell Sci.117:5965-73.
[36]San Miguel Fraile P, Gomez de Maria C, Donis Quintairos L, Carrera Vazquez A, Iglesias Martinez P, Barreiro Barbosa MJ. Expresion of E-cadherin and catenins in urothelial carcinomas. Actas Urol Esp.31(4):355-60 (2007).
[37]Oxford G, Theodorescu D. The role of RAS superfamily proteins in bladder cancer progression. J Urol; 170:1987-1993 (2003).
[38]Johnson M, Toms S. Mitogenic signal transduction pathways in meningiomas:novel targets for meningioma chemotherapy? J. Neuropathol. Exp. Neurol.64:1029-1036 (2005).
[39]Wu X, Obata T, Khan Q, Highshaw RA, DeVere White R, Sweeney C. The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion. Br. J. Urol. Int.93:143-150(2004).
[40]Tanaka M, Koul D, Davies MA, Liebert M, Steck PA, Grossman HB. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Oncogene 19:5406-5412 (2000).
[41]Nakanishi C, Toi M. Nuclear factor-KB inhibitors as sensitizers to anticancer drugs. Nat. Rev. Cancer 5:297-309 (2005).
[42]Muller M. Telomerase:its clinical relevance in the diagnosis of bladder cancer. Oncogene,21(4),650-565 (2002).
[43]Kyo SH, Takakura M, Fujiwara T, Inoue M. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci.,99(8), 1528-1538(2008).
[44]Sharrocks, A.D. The ETS-domain transcription factor family. Nat. Rev. Mol. Cell Biol. 2:827-837 (2001).
[45]Maroulakou, I.G. and Bowe. D.B. Expression and function of Ets transcription factors in mammalian development:a regulatory network. Oncogene 19:6432-6442 (2000).
[46]Maida Y, Kyo S, Kanaya T, Wang Z, Yatabe N, Tanaka M, Nakamura M, Ohmichi M, Gotoh N,, Murakami S, Inoue M. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Oncogene, 21(26),4071-4079 (2002).
[47]Yang G, Thompson JA, Fang B, Liu J. Silencing of H-ras gene expression by retrovirus-mediated siRNA decreases transformation efficiency and tumorgrowth in a model of human ovarian cancer. Oncogene.22(36):5694-701 (2003).
[48]Martinez L A, Naguibneva I, Lehrmann H, Vervisch A, Tchenio T, Lozano G, and Annick Harel-Bellan A. Synthetic small inhibiting RNAs:Efficient tools to inactivate oncogenic mutations and restore p53 pathways. Proc Natl Acad Sci USA,99(23): 14849—14854 (2002).
[49]Shen J, Samul R, Silva R L, et al. Suppression of ocular neovascu-larization with siRNA targeting VEGF receptor 1. Gene Ther,13(3):225-234 (2006).
[50]Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411:494—498(2001).
[51]Hannon CJ.RNA interference. Nature,418(6894):244-251 (2002).
[52]Brummelkamp T R, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science,296:550—553 (2002).
[53]Fleming J B, Shen G L, Holloway S E. Molecular consequences of silencing mutant K-ras in pancreatic cancer cells:justification for K-ras-directed therapy. Mol Cancer Res,3(7):413-423 (2005).
[54]Chernolovskaya EL, Zenkova MA. Chemical modification of siRNA. Curr Opin Mol Ther.12(2):158-67 (2010).
[55]Oh YK, Park TG. siRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 61(10):850-862(2009).
[56]Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell,121(2),179-193 (2005).
[57]Fredericks WJ, Wang H, Zheng Y, Boyer J, Schullery D, Aqui N, Lal, P, Tomaszewski J, McGarvey T, Malkowicz SB. Elevated TERE1 protein induces cytokine expression in J82 bladder cancer and human immune cells. AUA Orlando, FL (2008).
[58]Fredericks WJ, Wang H, Sepulveda J, McGarvey T, Malkowicz SB. TERE1/UBAID1 and TBL2 proteins Regulate cholesterol levels in bladder cancer cells. Accepted AUA Chicago (2009).
[59]Tsuruta, H., Kishimoto, H., Sasaki, T., Horie, Y., Natsui, M., Shibata, Y., Hamada, K., Yajima, N., Kawahara, K., Sasaki, M., et al. Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients. Cancer Res.66:8389-8396 (2006).
[60]Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH and Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science,275,1943-1947 (1997).
[61]Cairns, P., Evron, E., Okami, K., Halachmi, N., Esteller, M., Herman, J.G., Bose, S., Wang, S.I., Parsons, R., and Sidransky, D. Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene 16:3215-3218 (1998).
[62]Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, Wang X, Shen TH, Matos T, Shen MM, Cordon-Cardo C, Abate-Shen C. Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev..23(6):675-680 (2009).
[63]Cully, M., You, H., Levine, A.J., and Mak, T.W. Beyond PTEN mutations:The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat. Rev. Cancer 6: 184-192(2006).
[64]Abounader R. Interactions between PTEN and receptor tyrosine kinase pathways and their implications for glioma therapy. Expert Rev Anticancer Ther.9(2):235-245 (2009).
[1]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[2]McGravey, T.W., Nguyaen, T., Puthiyaveettil, R., Tomaszewski, J.E., and Malkowicz S.B. TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate,54,144-155(2003).
[3]Yellore VS, Khan MA, Bourla N, Rayner SA, Chen MC, Sonmez B, Momi RS, Sampat KM, Gorin MB, Aldave AJ. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol. Vis.,13,1777-1782 (2007).
[4]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10(2007).
[5]Van Went J, Wibaut F. Een zyeldzame erfelijke hoornvliesaandoening. Ned Tijdschr Geneesks 68:2996-2997 (1924).
[6]Weiss JS. Schnyder's dystrophy of the cornea. A Swede-Finn connection. Cornea 11: 93-101 (1992).
[7]Bron AJ. Corneal changes in the dislipoproteinaemias. Cornea 8:135-140 (1989).
[8]McCarthy M, Innis S, Dubord P, White V. Panstromal Schnyder corneal dystrophy. A clinical pathologic report with quantitative analysis of corneal lipid composition. Ophthalmology 101:895-901 (1994).
[9]Crispin S. Ocular lipid deposition and hyperlipoproteinaemia. Prog Retin Eye Res 21: 169-224(2002).
[10]Shearman AM, Hudson TJ, Andresen JM, Wu X, Sohn RL, Haluska F, Housman DE, Weiss JS. The gene for schnyder's crystalline corneal dystrophy maps to human chromosome 1p34.1-p36. Hum Mol Genet 5:1667-1672 (1996).
[11]Theendakara V, Tromp G, Kuivaniemi H, White PS, Panchal S, Cox J, Winters RS, Riebeling P, Tost F, Hoeltzenbein M, Tervo TM, Henn W, Denniger E, Krause M, Koksal M, Kargi S, Ugurbas SH, Latvala T, Shearman AM, Weiss JS. Fine mapping of the Schnyder's crystalline corneal dystrophy locus. Hum Genet 114:594-600 (2004).
[12]Xia, Y and Hong Ling, "TERE1/UBIAD1, a bridge between lipid metabolism and carcinogenesis", International Symposium on Lipid and Tissue Injury Nov26-29 2009, ChongQing,China page 75 (2009).
[13]Hong Ling, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Genetics Society of model organisms and human health seminar of China, Nanchang, Jiangxi, April 2010, Nanchang, P.R.China page 38 (2010).
[14]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, Lisch W, Henn W, Denninger E, Krause M, Wasson P, Ebenezer N, Mahurkar S, Nickerson ML. Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci.,48(11),5007-5012 (2007).
[15]McGravey, T.W., Nguyaen, T., and Malkowicz S.B. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J. cell. Biochem.,95,419-428 (2005).
[16]Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest.110:597-603 (2002).
[17]Heeren J, Beisiegel U, Grewal T. Apolipoprotein E recycling:implications for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol.26(3):442-8 (2006).
[18]Winter-Vann, A. M.& Casey, P. J. Post-prenylationprocessing enzymes as new targets in oncogenesis. Nature Rev. Cancer.5,405-412 (2005).
[19]Oldham, W. M., Van Eps, N., Preininger, A. M., Hubbell, W. L.& Hamm, H. E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nature Struct. Mol. Biol.9,772-777. (2006).
[20]Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science. 327(5961):46-50(2010).
[21]Radosavljevic V, Ilic M, Jankovic S, Djokic M. Diet in bladder cancer ethiopathogenesis. Acta Chir Iugosl.52(3):77-82 (2005).
[22]Moyad MA, Merrick GS. Cholesterol, cholesterol lowering agents/statins, and urologic disease:part I-knowing your numbers. Urol Nurs.26(2):156-159 (2006).
[23]Di Vizio D, Solomon KR, Freeman MR. Cholesterol and cholesterol-rich membranes in prostate cancer:an update. Tumori.94(5):633-639(2008).
[24]Hager MH, Solomon KR, Freeman MR. The role of cholesterol in prostate cancer. Curr Opin Clin Nutr Metab Care.9(4):379-385 (2006).
[25]Krycer JR, Kristiana I, Brown AJ. Cholesterol homeostasis in two commonly used human prostate cancer cell-lines, LNCaP and PC-3. PLoS One.4(12):e8496 (2009).
[26]Suvarna K, Stevenson D, Meganathan R, Hudspeth ME. Menaquinone (vitamin K2) biosynthesis:Localization and characterization of the menA gene from Escherichia coli. J Bacteriol 180:2782-2787 (1998).
[27]Melzer M, Heide L. Characterization of polyprenyldiphosphate:4-hydroxybenzoate polyprenyltransferase from Escherichia coli. Biochem Biophys Acta 1212:93-102 (1994).
[28]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, Lisch W, Dupps WJ Jr, White PS, Winters RS, Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu da W, Ebenezer N, Nickerson ML. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A.146(3):271-283 (2008).
[1]Resh MD. Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol.2(11):584-90 (2006).
[2]Panagiotis A, Konstantinopoulos, Michalia V,Karamouzis & Athanasios G,Papavassiliou. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nature Reviews Drug Discovery, 6,541-555 (2007).
[3]Sebastian Maurer-Stroh,Stefan Washietl and Frank Eisenhaber. Protein Prenyltransferases. Genome Biology.4:212(2003).
[4]Winter-Vann, A.M.& Casey, P.J. Post-prenylation-processing enzymes as new targets in oncogenesis. Nat. Rev. Cancer.5,405-412 (2005).
[5]Zhang, F. L.& Casey, P. J. Protein prenylation:molecular mechanisms and functional consequences. Annu. Rev. Biochem.65,241-269 (1996).
[6]Ashby, M. N. CaaX converting enzymes. Curr Opin. Lipidol.9,99-102 (1998).
[7]Casey, P. J., and M. C. Seabra. Protein prenyltransferases. J. Biol. Chem.271: 5289-5292(1996).
[8]Taylor, J.S., Reid, T.S., Terry, K.L., Casey, P.J.& Beese, L.S. Structure of mammalian. protein geranylgeranyltransferase type-Ⅰ. EMBOJ.22,5963-5974 (2003).
[9]Pei, J.& Grishin, N. V. Type Ⅱ CAAX prenyl endopeptidases belong to a novel superfamily of putative membrane-bound metalloproteases. Trends Biochem. Sci.26, 275-277(2001).
[10]Bourne, H. R., Sanders, D. A. and McCormick, F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 349,117-127 (1991).
[11]Choy, E., V. K. Chiu, J. Silletti, M. Feoktistov, T. Morimoto, D.Michaelson, I. E. Ivanov, and M. R. Philips. Endomembrane trafficking of ras:the CAAX motif targets proteins to the ER and Golgi. Cell.98:69-80 (1999).
[12]Malumbres, M.& Barbacid, M. RAS oncogenes:the first 30 years. Nature Rev. Cancer 3,459-465 (2003).
[13]Wright LP, Philips MR. Thematic review series:lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J Lipid Res. 47(5):883-91(2006).
[14]Colicelli, J. Human RAS superfamily proteins and related GTPases. Sci. STKE 2004, RE 13 (2004).
[15]Kimberly T. Lane ang Lorena S. Beese. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type 1. Journal of Lipid Research, 4,681-699(2006).
[16]Gelb MH, Brunsveld L, Hrycyna CA, Michaelis S, Tamanoi F, Van Voorhis WC, Waldmann H. Therapeutic intervention based on protein prenylation and associated modifications. Nature Chemical Biology 2,518-528 (2006).
[17]Svensson AW, Casey PJ, Young SG, Bergo MO. Genetic and pharmacologic analyses of the role of Icmt in Ras membrane association and function.Methods Enzymol.407:144-59 (2006)
[18]Mitchell DA, Vasudevan A, Linder ME, Deschenes RJ. Protein palmitoylation by a family of DHHC protein S-acyltransferases. J Lipid Res.47(6):1118-27 (2006).
[19]Baekkeskov S, Kanaani J. Palmitoylation cycles and regulation of protein function.Mol Membr Biol.26(1):42-54 (2009).
[20]Dietrich LE, Ungermann C. On the mechanism of protein palmitoylation. EMBO Rep.5(11):1053-1057 (2004).
[21]Magee, T., and M. C. Seabra. Fatty acylation and prenylation of proteins:what's hot in fat. Curr. Opin. Cell Biol.17:190-196 (2005).
[22]Leung, K.F., Baron, R.& Seabra, M.C. Thematic review series:lipid posttranslational modifications. Geranylgeranylation of Rab GTPases. J. Lipid Res. 47,467-475 (2006).
[23]Seabra, M. C., Y. Reiss, P. J. Casey, M. S. Brown, and J. L. Goldstein. Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell.65:429-434 (1991).
[24]Silvius, J.R. Mechanisms of Ras protein targeting in mammalian cells. J. Membr. Biol.190,83-92 (2002).
[25]Zerial, M., and H. McBride. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol.2:107-117(2001).
[26]Calero, M., C. Z. Chen, W. Zhu, N. Winand, K. A. Havas, P. M. Gilbert, C. G. Burd, and R. N. Collins. Dual prenylation is required for rab protein localization and function. Mol. Biol. Cell.14:1852-1867 (2003).
[27]Andres DA, Milatovich A, Ozcelik T, Wenzlau JM, Brown MS, Goldstein JL, Francke U:cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences. Genomics.18:105-112(1993).
[28]Maurer-Stroh S, Washietl S, Eisenhaber F. Protein prenyltransferases. Genome Biol. 4(4):212(2003).
[29]Liang PH, Ko TP, Wang AH:Structure, mechanism and function of prenyltransferases. Eur J Biochem.269:3339-3354 (2002).
[30]Sinensky M:Recent advances in the study of prenylated proteins. Biochim Biophys Acta.1484:93-106(2000).
[31]Seabra MC, Reiss Y, Casey PJ, Brown MS, Goldstein JL. Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell.65(3):429-34 (1991).
[32]Zhang H, Grishin NV. The alpha-subunit of protein prenyltransferases is a member of the tetratricopeptide repeat family. Protein Sci.8:1658-1667(1999).
[33]Zhang, F. L., R. E. Diehl, N. E. Kohl, J. B. Gibbs, B. Giros, P. J. Casey, and C. A. Omer. cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I. J. Biol. Chem.269:3175-3180(1994).
[34]Dhawan P, Yang E, Kumar A, Mehta KD:Genetic complexity of the human
geranylgeranyltransferase I beta-subunit gene:a multigene family of pseudogenes derived from mis-spliced transcripts. Gene.210:9-15 (1998).
[35]Vandermoten S, Haubruge E, Cusson M. New insights into short-chain prenyltransferases:structural features, evolutionary history and potential for selective inhibition. Cell Mol Life Sci.66(23):3685-95(2009).
[36]Long, S.B., Casey, P.J.& Beese, L.S. Reaction path of protein farnesyltransferase at atomic resolution. Nature.419,645-650 (2002).
[37]Buckner, F. S., R. T. Eastman, J. L. Nepomuceno-Silva, E. C. Speelmon, P. J. Myler, W. C. Van Voorhis, and K. Yokoyama. Cloning, heterologous expression, and substrate specificities of protein farnesyltransferases from Trypanosoma cruzi and Leishmania major. Mol. Biochem. Parasitol.122:181-188 (2002).
[38]Nguyen UT, Guo Z, Delon C, Wu Y, Deraeve C, Franzel B, Bon RS, Blankenfeldt W, Goody RS, Waldmann H, Wolters D, Alexandrov K. Analysis of the eukaryotic prenylome by isoprenoid affinity tagging. Nat Chem Biol.5(4):227-35(2009).
[39]Pereira-Leal, J. B., and M. C. Seabra. The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J. Mol. Biol.301:1077-1087 (2000).
[40]Anant, J. S., L. Desnoyers, M. Machius, B. Demeler, J. C. Hansen, K. D. Westover, J. Deisenhofer, and M. C. Seabra. Mechanism of Rab geranylgeranylation:formation of the catalytic ternary complex. Biochemistry.37:12559-12568 (1998).
[41]Thoma, N. H., A. Iakovenko, A. Kalinin, H. Waldmann, R. S. Goody, and K. Alexandrov. Allosteric regulation of substrate binding and product release in geranylgeranyltransferase type Ⅱ. Biochemistry.40:268-274(2001).
[42]Tschantz, W. R., E. S. Furfine, and P. J. Casey. Substrate binding is required for release of product from mammalian protein farnesyltransferase. J. Biol. Chem.272: 9989-9993 (1997).
[43]Park, H-W., S. R. Boduluri, J. F. Moomaw, P. J. Casey, and L. S. Beese. Crystal structure of protein farnesyltransferase at 2.25 A0 resolution. Science.275: 1800-1804(1997).
[44]Brandt W, Brauer L, Gunnewich N, Kufka J, Rausch F, Schulze D, Schulze E, Weber R, Zakharova S, Wessjohann L. Molecular and structural basis of metabolic diversity mediated by prenyldiphosphate converting enzymes. Phytochemistry. 70(15-16):1758-75 (2009).
[45]Kral, A. M., R. E. Diehl, S. J. deSolms, T. M. Williams, N. E. Kohl, and C. A. Omer. Mutational analysis of conserved residues of the beta-subunit of human farnesyl:proteintransferase. J. Biol. Chem.272:27319-27323 (1997).
[46]Clausen, V. A., R. L. Edelstein, and M. D. Distefano. Stereochemical analysis of the reaction catalyzed by human protein geranylgeranyl transferase. Biochemistry.40: 3920-3930(2001).
[47]Seabra MC, Goldstein JL, Sudhof TC, Brown MS. Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys. J Biol Chem.267(20):14497-503 (1992).
[48]Dolence JM, Rozema DB, Poulter CD. Yeast protein farnesyltransferase. Site-directed mutagenesis of conserved residues in the beta-subunit. Biochemistry. 36(30):9246-52(1997).
[49]Wu YW, Goody RS, Abagyan R, Alexandrov K. Structure of the disordered C terminus of Rab7 GTPase induced by binding to the Rab geranylgeranyl transferase catalytic complex reveals the mechanism of Rab prenylation. J Biol Chem. 284(19):13185-92 (2009).
[50]Sasaki, T., A. Kikuchi, S. Araki, Y. Hata, M. Isomura, S. Kuroda, and Y. Takai. Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A, a ras p21-like GTPbinding protein. J. Biol. Chem.265:2333-2337 (1990).
[51]Seabra, M. C. Nucleotide dependence of Rab geranylgeranylation. Rab escort protein interacts preferentially with GDPbound Rab. J. Biol. Chem.271: 14398-14404(1996).
[52]Kloog, Y.& Cox, A. D. Prenyl-binding domains:potential targets for Ras inhibitors and anti-cancer drugs. Semin. Cancer Biol.14,253-261 (2004).
[53]Lurje G, Lenz HJ. EGFR signaling and drug discovery. Oncology.77(6):400-410 (2009).
[54]Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development:EGFR gene and cancer. FEBS J.277(2):301-8(2010).
[55]Daub, H., Specht, K.& Ullrich, A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nature Rev. Drug Discov.3,1001-1110 (2004).
[56]Gschwind, A., Fischer, O. M.& Ullrich, A. The discovery of receptor tyrosine kinases:targets for cancer therapy. Nature Rev. Cancer 4,361-370 (2004).
[57]Lebowitz, P. F., Casey, P. J., Prendergast, G. C.& Thissen, J. A. Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. J. Biol. Chem.272,15591-15594 (1997).
[58]Appels, N. M., Beijnen, J. H.& Schellens, J. H. Development of farnesyl transferase inhibitors:a review. Oncologist 10,565-578 (2005).
[59]Kloog, Y.& Cox, A. D. Prenyl-binding domains:potential targets for Ras inhibitors and anti-cancer drugs. Semin. Cancer Biol.14,253-261 (2004).
[60]Doll, R. J., Kirschmeier, P.& Bishop, W. R. Farnesyltransferase inhibitors as anticancer agents:critical crossroads. Curr. Opin. Drug Discov. Devel.7,478-486 (2004).
[61]Sebti, S. M.& Der, C. J. Searching for the elusive targets of farnesyltransferase inhibitors. Nature Rev. Cancer 3,945-951 (2003).
[62]Caraglia, M., Budillon, A., Tagliaferri, P., Marra, M., Abbruzzese, A.& Caponigro, F. Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms:preclinical and clinical implications. Curr. Drug Targets 6,301-323 (2005).
[63]Morgan, M. A. Combining prenylation inhibitors causes synergistic cytotoxicity, apoptosis and disruption of RAS-to-MAP kinase signalling in multiple myeloma cells. Br. J. Haematol.130,912-925 (2005).
[64]Basso, A. D., Kirschmeier, P.& Bishop, W. R. Lipid post-translational modifications. Farnesyl transferase inhibitors. J. Lipid Res.41,15-31 (2006).
[65]Law, B. K., Norgaard, P.& Moses, H. L. Farnesyltransferase inhibitor induces rapid growth arrest and blocks p70s6k activation by multiple stimuli. J. Biol. Chem.275, 10796-10801 (2000).
[66]Agrawal AG, Somani RR. Farnesyltransferase inhibitor as anticancer agent.Mini Rev Med Chem.9(6):638-52(2009).
[67]Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D. Phase Ⅲ trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J. Clin. Oncol.22, 1430-1438 (2004).
[68]Rao S, Cunningham D, de Gramont A, Scheithauer W, Smakal M, Humblet Y, Kourteva G, Iveson T, Andre T, Dostalova J, Illes A, Belly R, Perez-Ruixo JJ, Park YC, Palmer PA. Phase Ⅲ double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer.J.Clin. Oncol.22,3950-3957 (2004).
[69]Fouladi M, Nicholson HS, Zhou T, Laningham F, Helton KJ, Holmes E, Cohen K, Speights RA, Wright J, Pollack IF; Children's Oncology Group. A phase Ⅱ study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma:a Children's Oncology Group study. Cancer.110(11):2535-41(2007).
[70]Dalenc F, Doisneau-Sixou SF, Allal BC, Marsili S, Lauwers-Cances V, Chaoui K, Schiltz O, Monsarrat B, Filleron T, Renee N, Malissein E, Meunier E, Favre G, Roche H. Tipifarnib plus tamoxifen in tamoxifen-resistant metastatic breast cancer:a negative phase Ⅱ and screening of potential therapeutic markers by proteomic analysis. Clin Cancer Res.16(4):1264-71 (2010).
[71]Ravoet C, Mineur P, Robin V, Debusscher L, Bosly A, Andre M, El Housni H, Soree A, Bron D, Martiat P. Farnesyl transferase inhibitor (lonafarnib) in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia:a phase Ⅱ study.Ann Hematol.87(11):881-885 (2008).
[72]Dinsmore CJ, Bell IM. Inhibitors of farnesyltransferase and geranylgeranyltransferase-I for antitumor therapy:substrate-based design, conformational constraint and biological activity. Curr Top Med Chem. 3(10):1075-1093 (2003).
[73]Chiba Y, Sato S, Misawa M. GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. Int J Immunopathol Pharmacol.22(4):929-35 (2009).
[74]Huang XK, Meyer P, Li B, Raza A, Preisler HD. The effects of the farnesyl
transferase inhibitor FTI L-778,123 on normal, myelodysplastic, and myeloid leukemia bone marrow progenitor proliferation in vitro.Leuk Lymphoma. 44(1):157-164 (2003).
[75]Caraglia M, Budillon A, Tagliaferri P, Marra M, Abbruzzese A, Caponigro F. Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms:preclinical and clinical implications.Curr Drug Targets.6(3):301-323 (2005).
[76]Maiello MR, D'Alessio A, De Luca A, Carotenuto A, Rachiglio AM, Napolitano M, Cito L, Guzzo A, Normanno N. AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib.Breast Cancer Res Treat.102(3):275-282 (2007).
[77]Appels NM, Bolijn MJ, van Eijndhoven MA, Stephens TC, Beijnen JH, Schellens JH. Characterization of the in vitro activity of AZD3409, a novel prenyl transferase inhibitor. Cancer Chemother Pharmacol.2010 Mar 13.
[78]Appels NM, Bolijn MJ, Chan K, Stephens TC, Hoctin-Boes G, Middleton M, Beijnen JH, de Bono JS, Harris AL, Schellens JH. Phase I pharmacokinetic and pharmacodynamic study of the prenyl transferase inhibitor AZD3409 in patients with advanced cancer. Br J Cancer.98(12):1951-1958 (2008).
[79]Lu Q, Harrington EO, Newton J, Jankowich M, Rounds S. Inhibition of ICMT induces endothelial cell apoptosis through GRP94. Am J Respir Cell Mol Biol. 37(1):20-30(2007).
[80]Baron RA, Peterson YK, Otto JC, Rudolph J, Casey PJ. Time-dependent inhibition of isoprenylcysteine carboxyl methyltransferase by indole-based small molecules.Biochemistry.46(2):554-560 (2007).
[81]Winter-Vann AM, Baron RA, Wong W, dela Cruz J, York JD, Gooden DM, Bergo MO, Young SG, Toone EJ, Casey PJ. A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells.Proc Natl Acad Sci USA.102(12):4336-41 (2005).
[82]Donelson JL, Hodges HB, Macdougall DD, Henriksen BS, Hrycyna CA, Gibbs RA. Amide-substituted farnesylcysteine analogs as inhibitors of human isoprenylcysteine carboxyl methyltransferase.Bioorg Med Chem Lett.16(16):4420-3 (2006).
[83]Wang M, Tan W, Zhou J, Leow J, Go M, Lee HS, Casey PJ. A small molecule inhibitor of isoprenylcysteine carboxymethyltransferase induces autophagic cell death in PC3 prostate cancer cells.J Biol Chem.283(27):18678-84 (2008).
[84]Lu Q, Harrington EO, Hai CM, Newton J, Garber M, Hirase T, Rounds S. Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis. Mol. Biol. Cell 14,848-857 (2003).
[85]Fehrenbacher N, Bar-Sagi D, Philips M. Ras/MAPK signaling from endomembranes. Mol Oncol.3(4):297-307 (2009).
[86]Peterson, Y. K., Kelly, P., Weinbaum, C. A.&Casey, P. J. A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity. J. Biol. Chem.281,12445-12450(2006).
[87]Fritz G. Targeting the mevalonate pathway for improved anticancer therapy. Curr Cancer Drug Targets.9(5):626-38 (2009).
[2]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002. CA Cancer J. Clin.,55,74-108(2005).
[3]Mitral Anirban P. Cote Richard J. Molecular Pathogenesis and Diagnostics of
Bladder Cancer. Annu. Rev. Pathol. Mech. Dis..4:251-285 (2009).
[4]Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet, 374(9685):239-249 (2009).
[5]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[6]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10 (2007).
[7]Hong, L. and Rubin, G. M. "L(2)35Fc, a novel transmembrane protein required for suppression of melanotic tumors".39th Annual Drosophila Research Conference, March 25 to 29, Washington, DC. Page 128 (1998).
[8]McGravey, T.W., Nguyaen, T., and Malkowicz S.B. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J. cell. Biochem.,95,419-428 (2005).
[9]Panagiotis A, Konstantinopoulos,Michalia V,Karamouzis & Athanasios QPapavassiliou. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nature Reviews Drug Discovery, 6,541-555 (2007).
[1]Jemal Ahmedin, Siegel Rebecca, Ward Elizabeth, Hao Yongping, Xu Jiaquan, Thun Michael J. Cancer statistics,2009. CA Cancer J Clin.,59,225-249 (2009).
[2]Volanis D, Kadiyska T, Galanis A, Delakas D, Logotheti S, Zoumpourlis V. Environmental factors and genetic susceptibility promote urinary bladder cancer. Toxicol Lett.193(2):131-137 (2010).
[3]Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet,374(9685):239-249 (2009).
[4]Hartman M, Loy EY, Ku CS, Chia KS. Molecular epidemiology and its current clinical use in cancer management. Lancet Oncol.;11(4):383-390 (2010).
[5]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[6]McGravey, T.W., Nguyaen, T., Puthiyaveettil, R., Tomaszewski, J.E., and Malkowicz S.B. TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate,54,144-155(2003).
[7]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10(2007).
[8]Yellore VS, Khan MA, Bourla N, Rayner SA, Chen MC, Sonmez B, Momi RS, Sampat KM, Gorin MB, Aldave AJ. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol.Vis.,13,1777-1782 (2007).
[9]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, Lisch W, Henn W, Denninger E, Krause M, Wasson P, Ebenezer N, Mahurkar S, Nickerson ML. Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci.,48(11),5007-5012 (2007).
[10]Hong, L. and Rubin, G. M. "L(2)35Fc, a novel transmembrane protein required for suppression of melanotic tumors".39th Annual Drosophila Research Conference, March 25 to 29, Washington, DC. Page 128 (1998).
[11]Hong Ling, Xia, Y, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Hubei Genetics Meeting VIII, November 2009, Wuhan, Hubei, P.R.China page 140 (2009).
[12]Hong Ling, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Genetics Society of model organisms and human health seminar of China, Nanchang, Jiangxi, April 2010, Nanchang, P.R.China page 38 (2010).
[13]Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR. Telomerase catalytic subunit homologs from fission yeast and human. Science,277(5328),955-959 (1997).
[14]Hiyama E, Hiyama K. Telomerase as tumor marker. Cancer Lett.194(2):221-33 (2003).
[15]Kyo S, Inoue M. Complex regulatory mechanisms of telomerase activity in normal and cancer cells:how can we apply them for cancer therapy? Oncogene. 21(4):688-697(2002).
[16]Kyo S, Takakura M, Fujiwara T, Inoue M. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci.,99(8), 1528-1538(2008).
[17]Maida Y, Kyo S, Kanaya T, Wang Z, Yatabe N, Tanaka M, Nakamura M, Ohmichi M, Gotoh N,, Murakami S, Inoue M. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Oncogene, 21(26),4071-4079 (2002).
[18]Dwyer J, Li H, Xu D, Liu JP. Transcriptional regulation of telomerase activity:roles of the the Ets transcription factor family. Ann N Y Acad Sci. Oct;1114:36-47 (2007).
[19]Mitral Anirban P. Cote Richard J. Molecular Pathogenesis and Diagnostics of Bladder Cancer. Annu. Rev. Pathol. Mech. Dis.4:251-285 (2009).
[20]Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 100:57-70 (2000).
[21]Langzam L, Koren R, Gal R, Kugel V, Paz A, et al. Patterns of protein kinase C isoenzyme expression in transitional cell carcinoma of bladder:relation to degree of malignancy. Am. J. Clin. Pathol.116:377-85 (2001).
[22]Varga A, Czifra G, Tallai B, Nemeth T, Kovacs I, et al. Tumor grade-dependent alterations in the protein kinase C isoform pattern in urinary bladder carcinomas. Eur. Urol.46:462-65 (2004).
[23]Wu X, Obata T, Khan Q, Highshaw RA, De Vere White R, Sweeney C. The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion. Br. J. Urol.Int.93:143-50 (2001).
[24]Nakanishi C, Toi M. Nuclear factor-κB inhibitors as sensitizers to anticancer drugs. Nat. Rev. Cancer 5:297-309 (2005).
[25]Jebar AH, Hurst CD, Tomlinson DC, Johnston C, Taylor CF, Knowles MA. FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 24:5218-5225 (2005).
[26]Mitra AP, Lin H, Datar RH, Cote RJ. Molecular biology of bladder cancer:prognostic and clinical implications. Clin. Genitourin. Cancer 5:67-77 (2006).
[27]Kramer C, Klasmeyer K, Bojar H, Schulz WA, Ackermann R, Grimm MO. Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB 1 expression in bladder cancer and their relation to clinical outcome. Cancer 109:2016-24 (2007).
[28]Memon AA, Sorensen BS, Meldgaard P, Fokdal L, Thykjaer T, Nexo E. The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4:a study in bladder cancer patients. Br. J. Cancer 94:1703-9 (2006).
[29]A.P. Mitra, R.H. Datar and R.J. Cote, Molecular pathways in invasive bladder cancer: New insights into mechanisms, progression, and target identification, J Clin Oncol 24. 5552-5564 (2006).
[30]Knowles MA. Molecular subtypes of bladder cancer:Jekyll and Hyde or chalk and cheese? Carcinogenesis.27:361-73 (2006).
[31]Hu, M., and Polyak, K. Microenvironmental regulation of cancer development. Curr. Opin. Genet. Dev.18,27-34 (2008).
[32]Yang Jing, Chun Liu, Junmin Xu, Liya WangA. Novel UBIAD1 mutation identified in a Chinese family with Schnder crystalline corneal dystrophy. Molecular Vision.1463-1469(2009).
[33]Nagai H, Negrini M, Carter SL, Gillum DR, Rosenberg AL, Schwartz GF and Croce CM. Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer. Cancer Res.,55,1752-1757 (1995).
[34]Praml C, Finke LH, Herfarth C, Schlag P, Schwab M and Amler L. Deletion mapping defines different regions in 1p34.2-pter that may harbor genetic information related to human colorectal cancer. Oncogene,11,1357-1362 (1995).
[35]Bieche I, Khodja A, Lidereau R. Deletion mapping in breast tumor cell lines points to two distinct tumor-suppressor genes in the 1p32-pter region, one of deleted regions (1p36.2) being located within the consensus region of LOH in neuroblastoma. Oncol Rep.5(1):267-72 (1998).
[36]Hogarty MD, Maris JM, White PS, Guo C, Brodeur GM. Analysis of genomic imprinting at 1p35-36 in neuroblastoma. Med Pediatr Oncol.36(1):52-55 (2001).
[37]Ebrahimi SA, Wang EH, Wu A, Schreck RR, Passaro Jr E and Sawicki MP. Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors. Cancer Res.,59, 311-315(1999).
[38]Jiang H, Orr A, Guernsey DL, Robitaille J, Asselin G, Samuels ME, Dube MP. Application of homozygosity haplotype analysis to genetic mapping with high-density SNP genotype data. PLoS One.4(4):e5280 (2009).
[39]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, Lisch W, Dupps WJ Jr, White PS, Winters RS, Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu da W, Ebenezer N, Nickerson ML. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A.146(3):271-283 (2008).
[40]Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011-2015 (1994).
[41]Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell.97:527-538 (1999).
[42]Dwyer JM, Liu JP. Ets2 transcription factor, telomerase activity and breast cancer. Clin Exp Pharmacol Physiol.37(1):83-87 (2010).
[43]Panagiotis A, Konstantinopoulos, Michalia V, Karamouzis & Athanasios G, Papavassiliou. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nature Reviews Drug Discovery 6,541-555 (2007).
[44]Oldham, W. M., Van Eps, N., Preininger, A. M., Hubbell, W. L.& Hamm, H. E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nature Struct. Mol. Biol.9,772-777 (2006).
[45]Michael H Gelb,Lucas Brunsveld,Christine A Hrycyna,Susan Michaelis,Fuyuhiko Tamanoi,Wesley C Van Voorhis&Herbert Waldmann. Therapeutic intervention based on protein prenylation and associated modifications. Nature Chemical Biology. 2,518-528(2006).
[46]U.R. Rapp, M.D. Goldsborough, G.E. Mark, T.I. Bonner, J. Groffen, F.H. Reynolds Jr., J.R. Stephenson, Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus, Proc. Natl. Acad. Sci. U. S. A.804218-4222 (1983).
[47]T. Bonner, S.J. O'Brien, W.G. Nash, U.R. Rapp, C.C. Morton, P. Leder,The human homologs of the raf (mil) oncogene are located on human chromosomes 3 and 4, Science.223,71-74(1984).
[48]C. Hagemann, U.R. Rapp, Isotype-specific functions of Raf kinases, Exp.Cell Res.253, 34-46(1999).
[49]C. Wellbrock, M. Karasarides, R. Marais, The RAF proteins take centre stage, Nat. Rev., Mol. Cell Biol.5,875-885 (2004).
[50]K. Mercer, S. Giblett, A. Oakden, J. Brown, R. Marais, C. Pritchard,A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression, Oncogene 24,5207-5217 (2005).
[51]Y.H. Hwang, J.Y. Choi, S. Kim, E.S. Chung, T. Kim, S.S. Koh, B. Lee,S.H. Bae, J. Kim, Y.M. Park, Over-expression of c-raf-1 protooncogene in liver cirrhosis and hepatocellular carcinoma, Hepatol. Res.29,113-121(2004).
[52]R. Mukherjee, J.M. Bartlett, N.S. Krishna, M.A. Underwood, J. Edwards, Raf-1 expression may influence progression to androgen insensitive prostate cancer, Prostate 64,101-107 (2005).
[53]S. Wang, R.N. Ghosh, S.P. Chellappan, Raf-1 physically interacts with Rb and regulates its function:a link between mitogenic signaling and cell cycle regulation, Mol. Cell. Biol.18,7487-7498 (1998).
[54]E.T. Keller, Z. Fu, M. Brennan, The biology of a prostate cancer metastasis suppressor protein:Raf kinase inhibitor protein, J. Cell. Biochem.94,273-278 (2005).
[55]V. Emuss, M. Garnett, C. Mason, R. Marais, Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF, Cancer Res.65,9719-9726 (2005).
[56]Karreth FA, DeNicola GM, Winter SP, Tuveson DA. C-Raf inhibits MAPK activation and transformation by B-Raf (V600E). Mol Cell.36(3):477-486(2009).
[1]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[2]McGravey, T.W., Nguyaen, T., Puthiyaveettil, R., Tomaszewski, J.E., and Malkowicz S.B. TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate,54,144-155 (2003).
[3]Hong, L. and Rubin, G. M. "L(2)35Fc, a novel transmembrane protein required for suppression of melanotic tumors".39th Annual Drosophila Research Conference, March 25 to 29, Washington, DC. Page 128 (1998).
[4]Xia, Y and Hong Ling, "TERE1/UBIAD1, a bridge between lipid metabolism and carcinogenesis", International Symposium on Lipid and Tissue Injury Nov26-29 2009, ChongQing,China page 75 (2009).
[5]Hong Ling, Xia, Y, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Hubei Genetics Meeting Ⅷ, November 2009, Wuhan, Hubei, P.R.China page 140 (2009).
[6]Hong Ling, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Genetics Society of model organisms and human health seminar of China, Nanchang, Jiangxi, April 2010, Nanchang, P.R.China page 38 (2010).
[7]Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet,374(9685):239-249 (2009).
[8]Wu XR. Urothelial tumorigenesis:a tale of divergent pathways. Nat. Rev. Cancer. 5:713-25 (2005).
[9]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, Lisch W, Henn W, Denninger E, Krause M, Wasson P, Ebenezer N, Mahurkar S, Nickerson ML Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci.,48(11),5007-5012 (2007).
[10]Yellore VS, Khan MA, BourlaN, Rayner SA, Chen MC, Sonmez B, Momi RS, Sampat KM, Gorin MB, Aldave AJ. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol. Vis.,13,1777-1782 (2007).
[11]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, Lisch W, Dupps WJ Jr, White PS, Winters RS, Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu da W, Ebenezer N, Nickerson ML. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A.146(3):271-283 (2008).
[12]McGravey, T.W., Nguyaen, T., and Malkowicz S.B. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J. cell. Biochem.,95,419-428 (2005).
[13]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10(2007).
[14]Zhang, F. L.& Casey, P. J. Protein prenylation:molecular mechanisms and functional consequences. Annu. Rev. Biochem.65,241-269 (1996).
[15]Winter-Vann, A. M.& Casey, P. J. Post-prenylationprocessing enzymes as new targets in oncogenesis. Nature Rev. Cancer.5,405-412 (2005).
[16]Oldham, W. M., Van Eps, N., Preininger, A. M., Hubbell, W. L.& Hamm, H. E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nature Struct. Mol. Biol.9,772-777. (2006).
[17]Pfeffer, S.& Aivazian, D. Targeting Rab GTPases to distinct membrane compartments. Nature Rev. Mol. Cell Biol.5,886-896 (2004).
[18]Doll, R. J., Kirschmeier, P.& Bishop, W. R. Farnesyltransferase inhibitors as anticancer agents:critical crossroads. Curr. Opin. Drug Discov. Devel.7,478-486 (2004).
[19]Sebti, S. M.& Der, C. J. Searching for the elusive targets of farnesyltransferase inhibitors. Nature Rev. Cancer 3,945-951 (2003).
[20]Knowles MA. What we could do now:molecular pathology of bladder cancer. Mol. Pathol.54:215-221 (2001).
[21]Mitra AP, Cote RJ. Searching for novel therapeutics and targets:insights from clinical trials. Urol. Oncol.25:341-343 (2007).
[22]Mitral Anirban P. Cote Richard J. Molecular Pathogenesis and Diagnostics of Bladder Cancer. Annu. Rev. Pathol. Mech. Dis.4:251-285 (2009).
[23]Hanahan D,Weinberg RA. The hallmarks of cancer. Cell 100:57-70 (2000).
[24]Mitra AP, Lin H, Datar RH, Cote RJ. Molecular biology of bladder cancer:prognostic and clinical implications. Clin. Genitourin. Cancer 5:67-77 (2006).
[25]Lopez-Knowles E, Hernandez S, Kogevinas M, Lloreta J, Amoros A, Tardon A, Carrato A, Kishore S, Serra C, Malats N, Real FX; EPICURO Study Investigators. The p53 pathway and outcome among patients with T1G3 bladder tumors. Clin Cancer Res. 12(20 Pt 1):6029-6036 (2006).
[26]Liukkonen T, Rajala P, Raitanen M, Rintala E, Kaasinen E, Lipponen P. Prognostic value of MIB-1 score, p53, EGFr, mitotic index and papillary status in primary superficial (Stage pTa/T1) bladder cancer:a prospective comparative study. Eur. Urol. 36:393-400(1999).
[27]Chatterjee SJ, Datar R, Youssefzadeh D, George B, Goebell PJ, Stein JP, Young L, Shi SR, Gee C, Groshen S, Skinner DG, Cote RJ. Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma, J Clin Oncol 22. 1007-1013 (2004).
[28]Shariat SF, Youssef RF, Gupta A, Chade DC, Karakiewicz PI, Isbarn H, Jeldres C, Sagalowsky AI, Ashfaq R, Lotan Y. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol.183(5):1744-1750 (2010).
[29]Birkhahn M, Mitra AP, Cote RJ. Molecular markers for bladder cancer:the road to a multimarker approach. Expert Rev. Anticancer Ther. 7:1717-1727 (2007).
[30]Wolf HK, Stober C, Hohenfellner R, Leissner J. Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumor Biol.22:328-336 (2001).
[31]Maluf FC, Cordon-Cardo C, Verbel DA, Satagopan JM, Boyle MG, et al. Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment. Ann. Oncol.17:1677-86(2006).
[32]Gabriel U, Bolenz C, Becker A, Schaaf A, Steidler A, Trojan L, Weiss C, Michel MS. Evaluation of cytotoxic effects induced by bcl-2 and bcl-xL antisense-oligodeoxynucleotides in normal urothelium and transitional cell carcinoma. Oncol Rep.20(6):1419-1423 (2008).
[33]Soung YH, Lee JW, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH. BH3 domain mutation of proapoptotic genes Bad, Bmf and Bcl-G is rare in transitional cell carcinomas of the urinary bladder. Pathology 38:33-34 (2006).
[34]Chen FH, Crist SA, Zhang GJ, Iwamoto Y, See WA. Interleukin-6 production by human bladder tumor cell lines is up-regulated by bacillus Calmette-Guerin through nuclear factor-KB and Ap-1 via an immediate early pathway. J. Urol.168:786-97 (2002).
[35]Hess J, Angel P, Schorpp-Kistner M.2004. AP-1 subunits:quarrel and harmony among siblings.J. Cell Sci.117:5965-73.
[36]San Miguel Fraile P, Gomez de Maria C, Donis Quintairos L, Carrera Vazquez A, Iglesias Martinez P, Barreiro Barbosa MJ. Expresion of E-cadherin and catenins in urothelial carcinomas. Actas Urol Esp.31(4):355-60 (2007).
[37]Oxford G, Theodorescu D. The role of RAS superfamily proteins in bladder cancer progression. J Urol; 170:1987-1993 (2003).
[38]Johnson M, Toms S. Mitogenic signal transduction pathways in meningiomas:novel targets for meningioma chemotherapy? J. Neuropathol. Exp. Neurol.64:1029-1036 (2005).
[39]Wu X, Obata T, Khan Q, Highshaw RA, DeVere White R, Sweeney C. The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion. Br. J. Urol. Int.93:143-150(2004).
[40]Tanaka M, Koul D, Davies MA, Liebert M, Steck PA, Grossman HB. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Oncogene 19:5406-5412 (2000).
[41]Nakanishi C, Toi M. Nuclear factor-KB inhibitors as sensitizers to anticancer drugs. Nat. Rev. Cancer 5:297-309 (2005).
[42]Muller M. Telomerase:its clinical relevance in the diagnosis of bladder cancer. Oncogene,21(4),650-565 (2002).
[43]Kyo SH, Takakura M, Fujiwara T, Inoue M. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci.,99(8), 1528-1538(2008).
[44]Sharrocks, A.D. The ETS-domain transcription factor family. Nat. Rev. Mol. Cell Biol. 2:827-837 (2001).
[45]Maroulakou, I.G. and Bowe. D.B. Expression and function of Ets transcription factors in mammalian development:a regulatory network. Oncogene 19:6432-6442 (2000).
[46]Maida Y, Kyo S, Kanaya T, Wang Z, Yatabe N, Tanaka M, Nakamura M, Ohmichi M, Gotoh N,, Murakami S, Inoue M. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Oncogene, 21(26),4071-4079 (2002).
[47]Yang G, Thompson JA, Fang B, Liu J. Silencing of H-ras gene expression by retrovirus-mediated siRNA decreases transformation efficiency and tumorgrowth in a model of human ovarian cancer. Oncogene.22(36):5694-701 (2003).
[48]Martinez L A, Naguibneva I, Lehrmann H, Vervisch A, Tchenio T, Lozano G, and Annick Harel-Bellan A. Synthetic small inhibiting RNAs:Efficient tools to inactivate oncogenic mutations and restore p53 pathways. Proc Natl Acad Sci USA,99(23): 14849—14854 (2002).
[49]Shen J, Samul R, Silva R L, et al. Suppression of ocular neovascu-larization with siRNA targeting VEGF receptor 1. Gene Ther,13(3):225-234 (2006).
[50]Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411:494—498(2001).
[51]Hannon CJ.RNA interference. Nature,418(6894):244-251 (2002).
[52]Brummelkamp T R, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science,296:550—553 (2002).
[53]Fleming J B, Shen G L, Holloway S E. Molecular consequences of silencing mutant K-ras in pancreatic cancer cells:justification for K-ras-directed therapy. Mol Cancer Res,3(7):413-423 (2005).
[54]Chernolovskaya EL, Zenkova MA. Chemical modification of siRNA. Curr Opin Mol Ther.12(2):158-67 (2010).
[55]Oh YK, Park TG. siRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 61(10):850-862(2009).
[56]Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell,121(2),179-193 (2005).
[57]Fredericks WJ, Wang H, Zheng Y, Boyer J, Schullery D, Aqui N, Lal, P, Tomaszewski J, McGarvey T, Malkowicz SB. Elevated TERE1 protein induces cytokine expression in J82 bladder cancer and human immune cells. AUA Orlando, FL (2008).
[58]Fredericks WJ, Wang H, Sepulveda J, McGarvey T, Malkowicz SB. TERE1/UBAID1 and TBL2 proteins Regulate cholesterol levels in bladder cancer cells. Accepted AUA Chicago (2009).
[59]Tsuruta, H., Kishimoto, H., Sasaki, T., Horie, Y., Natsui, M., Shibata, Y., Hamada, K., Yajima, N., Kawahara, K., Sasaki, M., et al. Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients. Cancer Res.66:8389-8396 (2006).
[60]Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH and Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science,275,1943-1947 (1997).
[61]Cairns, P., Evron, E., Okami, K., Halachmi, N., Esteller, M., Herman, J.G., Bose, S., Wang, S.I., Parsons, R., and Sidransky, D. Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene 16:3215-3218 (1998).
[62]Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, Wang X, Shen TH, Matos T, Shen MM, Cordon-Cardo C, Abate-Shen C. Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev..23(6):675-680 (2009).
[63]Cully, M., You, H., Levine, A.J., and Mak, T.W. Beyond PTEN mutations:The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat. Rev. Cancer 6: 184-192(2006).
[64]Abounader R. Interactions between PTEN and receptor tyrosine kinase pathways and their implications for glioma therapy. Expert Rev Anticancer Ther.9(2):235-245 (2009).
[1]McGravey, T.W., Nguyaen, T., Tomaszewski, J.E., Monson, F.C. and Malkowicz S.B. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene,20,1042-1051 (2001).
[2]McGravey, T.W., Nguyaen, T., Puthiyaveettil, R., Tomaszewski, J.E., and Malkowicz S.B. TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate,54,144-155(2003).
[3]Yellore VS, Khan MA, Bourla N, Rayner SA, Chen MC, Sonmez B, Momi RS, Sampat KM, Gorin MB, Aldave AJ. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol. Vis.,13,1777-1782 (2007).
[4]Orr A, Dube MP, Marcadier J, Jiang H, Federico A, George S, Seamone C, Andrews D, Dubord P, Holland S, Provost S, Mongrain V, Evans S, Higgins B, Bowman S, Guernsey D, Samuels M. Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy, PlosOne,8, e6851-10(2007).
[5]Van Went J, Wibaut F. Een zyeldzame erfelijke hoornvliesaandoening. Ned Tijdschr Geneesks 68:2996-2997 (1924).
[6]Weiss JS. Schnyder's dystrophy of the cornea. A Swede-Finn connection. Cornea 11: 93-101 (1992).
[7]Bron AJ. Corneal changes in the dislipoproteinaemias. Cornea 8:135-140 (1989).
[8]McCarthy M, Innis S, Dubord P, White V. Panstromal Schnyder corneal dystrophy. A clinical pathologic report with quantitative analysis of corneal lipid composition. Ophthalmology 101:895-901 (1994).
[9]Crispin S. Ocular lipid deposition and hyperlipoproteinaemia. Prog Retin Eye Res 21: 169-224(2002).
[10]Shearman AM, Hudson TJ, Andresen JM, Wu X, Sohn RL, Haluska F, Housman DE, Weiss JS. The gene for schnyder's crystalline corneal dystrophy maps to human chromosome 1p34.1-p36. Hum Mol Genet 5:1667-1672 (1996).
[11]Theendakara V, Tromp G, Kuivaniemi H, White PS, Panchal S, Cox J, Winters RS, Riebeling P, Tost F, Hoeltzenbein M, Tervo TM, Henn W, Denniger E, Krause M, Koksal M, Kargi S, Ugurbas SH, Latvala T, Shearman AM, Weiss JS. Fine mapping of the Schnyder's crystalline corneal dystrophy locus. Hum Genet 114:594-600 (2004).
[12]Xia, Y and Hong Ling, "TERE1/UBIAD1, a bridge between lipid metabolism and carcinogenesis", International Symposium on Lipid and Tissue Injury Nov26-29 2009, ChongQing,China page 75 (2009).
[13]Hong Ling, "Heixuedian, the Drosophila ortholog of TERE1/UBIAD1, encodes a novel membrane-bound prenyltransferase suppressing malignant blood tumor", Genetics Society of model organisms and human health seminar of China, Nanchang, Jiangxi, April 2010, Nanchang, P.R.China page 38 (2010).
[14]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, Lisch W, Henn W, Denninger E, Krause M, Wasson P, Ebenezer N, Mahurkar S, Nickerson ML. Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci.,48(11),5007-5012 (2007).
[15]McGravey, T.W., Nguyaen, T., and Malkowicz S.B. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J. cell. Biochem.,95,419-428 (2005).
[16]Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest.110:597-603 (2002).
[17]Heeren J, Beisiegel U, Grewal T. Apolipoprotein E recycling:implications for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol.26(3):442-8 (2006).
[18]Winter-Vann, A. M.& Casey, P. J. Post-prenylationprocessing enzymes as new targets in oncogenesis. Nature Rev. Cancer.5,405-412 (2005).
[19]Oldham, W. M., Van Eps, N., Preininger, A. M., Hubbell, W. L.& Hamm, H. E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nature Struct. Mol. Biol.9,772-777. (2006).
[20]Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science. 327(5961):46-50(2010).
[21]Radosavljevic V, Ilic M, Jankovic S, Djokic M. Diet in bladder cancer ethiopathogenesis. Acta Chir Iugosl.52(3):77-82 (2005).
[22]Moyad MA, Merrick GS. Cholesterol, cholesterol lowering agents/statins, and urologic disease:part I-knowing your numbers. Urol Nurs.26(2):156-159 (2006).
[23]Di Vizio D, Solomon KR, Freeman MR. Cholesterol and cholesterol-rich membranes in prostate cancer:an update. Tumori.94(5):633-639(2008).
[24]Hager MH, Solomon KR, Freeman MR. The role of cholesterol in prostate cancer. Curr Opin Clin Nutr Metab Care.9(4):379-385 (2006).
[25]Krycer JR, Kristiana I, Brown AJ. Cholesterol homeostasis in two commonly used human prostate cancer cell-lines, LNCaP and PC-3. PLoS One.4(12):e8496 (2009).
[26]Suvarna K, Stevenson D, Meganathan R, Hudspeth ME. Menaquinone (vitamin K2) biosynthesis:Localization and characterization of the menA gene from Escherichia coli. J Bacteriol 180:2782-2787 (1998).
[27]Melzer M, Heide L. Characterization of polyprenyldiphosphate:4-hydroxybenzoate polyprenyltransferase from Escherichia coli. Biochem Biophys Acta 1212:93-102 (1994).
[28]Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, Lisch W, Dupps WJ Jr, White PS, Winters RS, Kim C, Rapuano CJ, Sutphin J, Reidy J, Hu FR, Lu da W, Ebenezer N, Nickerson ML. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A.146(3):271-283 (2008).
[1]Resh MD. Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol.2(11):584-90 (2006).
[2]Panagiotis A, Konstantinopoulos, Michalia V,Karamouzis & Athanasios G,Papavassiliou. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nature Reviews Drug Discovery, 6,541-555 (2007).
[3]Sebastian Maurer-Stroh,Stefan Washietl and Frank Eisenhaber. Protein Prenyltransferases. Genome Biology.4:212(2003).
[4]Winter-Vann, A.M.& Casey, P.J. Post-prenylation-processing enzymes as new targets in oncogenesis. Nat. Rev. Cancer.5,405-412 (2005).
[5]Zhang, F. L.& Casey, P. J. Protein prenylation:molecular mechanisms and functional consequences. Annu. Rev. Biochem.65,241-269 (1996).
[6]Ashby, M. N. CaaX converting enzymes. Curr Opin. Lipidol.9,99-102 (1998).
[7]Casey, P. J., and M. C. Seabra. Protein prenyltransferases. J. Biol. Chem.271: 5289-5292(1996).
[8]Taylor, J.S., Reid, T.S., Terry, K.L., Casey, P.J.& Beese, L.S. Structure of mammalian. protein geranylgeranyltransferase type-Ⅰ. EMBOJ.22,5963-5974 (2003).
[9]Pei, J.& Grishin, N. V. Type Ⅱ CAAX prenyl endopeptidases belong to a novel superfamily of putative membrane-bound metalloproteases. Trends Biochem. Sci.26, 275-277(2001).
[10]Bourne, H. R., Sanders, D. A. and McCormick, F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 349,117-127 (1991).
[11]Choy, E., V. K. Chiu, J. Silletti, M. Feoktistov, T. Morimoto, D.Michaelson, I. E. Ivanov, and M. R. Philips. Endomembrane trafficking of ras:the CAAX motif targets proteins to the ER and Golgi. Cell.98:69-80 (1999).
[12]Malumbres, M.& Barbacid, M. RAS oncogenes:the first 30 years. Nature Rev. Cancer 3,459-465 (2003).
[13]Wright LP, Philips MR. Thematic review series:lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J Lipid Res. 47(5):883-91(2006).
[14]Colicelli, J. Human RAS superfamily proteins and related GTPases. Sci. STKE 2004, RE 13 (2004).
[15]Kimberly T. Lane ang Lorena S. Beese. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type 1. Journal of Lipid Research, 4,681-699(2006).
[16]Gelb MH, Brunsveld L, Hrycyna CA, Michaelis S, Tamanoi F, Van Voorhis WC, Waldmann H. Therapeutic intervention based on protein prenylation and associated modifications. Nature Chemical Biology 2,518-528 (2006).
[17]Svensson AW, Casey PJ, Young SG, Bergo MO. Genetic and pharmacologic analyses of the role of Icmt in Ras membrane association and function.Methods Enzymol.407:144-59 (2006)
[18]Mitchell DA, Vasudevan A, Linder ME, Deschenes RJ. Protein palmitoylation by a family of DHHC protein S-acyltransferases. J Lipid Res.47(6):1118-27 (2006).
[19]Baekkeskov S, Kanaani J. Palmitoylation cycles and regulation of protein function.Mol Membr Biol.26(1):42-54 (2009).
[20]Dietrich LE, Ungermann C. On the mechanism of protein palmitoylation. EMBO Rep.5(11):1053-1057 (2004).
[21]Magee, T., and M. C. Seabra. Fatty acylation and prenylation of proteins:what's hot in fat. Curr. Opin. Cell Biol.17:190-196 (2005).
[22]Leung, K.F., Baron, R.& Seabra, M.C. Thematic review series:lipid posttranslational modifications. Geranylgeranylation of Rab GTPases. J. Lipid Res. 47,467-475 (2006).
[23]Seabra, M. C., Y. Reiss, P. J. Casey, M. S. Brown, and J. L. Goldstein. Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell.65:429-434 (1991).
[24]Silvius, J.R. Mechanisms of Ras protein targeting in mammalian cells. J. Membr. Biol.190,83-92 (2002).
[25]Zerial, M., and H. McBride. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol.2:107-117(2001).
[26]Calero, M., C. Z. Chen, W. Zhu, N. Winand, K. A. Havas, P. M. Gilbert, C. G. Burd, and R. N. Collins. Dual prenylation is required for rab protein localization and function. Mol. Biol. Cell.14:1852-1867 (2003).
[27]Andres DA, Milatovich A, Ozcelik T, Wenzlau JM, Brown MS, Goldstein JL, Francke U:cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences. Genomics.18:105-112(1993).
[28]Maurer-Stroh S, Washietl S, Eisenhaber F. Protein prenyltransferases. Genome Biol. 4(4):212(2003).
[29]Liang PH, Ko TP, Wang AH:Structure, mechanism and function of prenyltransferases. Eur J Biochem.269:3339-3354 (2002).
[30]Sinensky M:Recent advances in the study of prenylated proteins. Biochim Biophys Acta.1484:93-106(2000).
[31]Seabra MC, Reiss Y, Casey PJ, Brown MS, Goldstein JL. Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell.65(3):429-34 (1991).
[32]Zhang H, Grishin NV. The alpha-subunit of protein prenyltransferases is a member of the tetratricopeptide repeat family. Protein Sci.8:1658-1667(1999).
[33]Zhang, F. L., R. E. Diehl, N. E. Kohl, J. B. Gibbs, B. Giros, P. J. Casey, and C. A. Omer. cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I. J. Biol. Chem.269:3175-3180(1994).
[34]Dhawan P, Yang E, Kumar A, Mehta KD:Genetic complexity of the human
geranylgeranyltransferase I beta-subunit gene:a multigene family of pseudogenes derived from mis-spliced transcripts. Gene.210:9-15 (1998).
[35]Vandermoten S, Haubruge E, Cusson M. New insights into short-chain prenyltransferases:structural features, evolutionary history and potential for selective inhibition. Cell Mol Life Sci.66(23):3685-95(2009).
[36]Long, S.B., Casey, P.J.& Beese, L.S. Reaction path of protein farnesyltransferase at atomic resolution. Nature.419,645-650 (2002).
[37]Buckner, F. S., R. T. Eastman, J. L. Nepomuceno-Silva, E. C. Speelmon, P. J. Myler, W. C. Van Voorhis, and K. Yokoyama. Cloning, heterologous expression, and substrate specificities of protein farnesyltransferases from Trypanosoma cruzi and Leishmania major. Mol. Biochem. Parasitol.122:181-188 (2002).
[38]Nguyen UT, Guo Z, Delon C, Wu Y, Deraeve C, Franzel B, Bon RS, Blankenfeldt W, Goody RS, Waldmann H, Wolters D, Alexandrov K. Analysis of the eukaryotic prenylome by isoprenoid affinity tagging. Nat Chem Biol.5(4):227-35(2009).
[39]Pereira-Leal, J. B., and M. C. Seabra. The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J. Mol. Biol.301:1077-1087 (2000).
[40]Anant, J. S., L. Desnoyers, M. Machius, B. Demeler, J. C. Hansen, K. D. Westover, J. Deisenhofer, and M. C. Seabra. Mechanism of Rab geranylgeranylation:formation of the catalytic ternary complex. Biochemistry.37:12559-12568 (1998).
[41]Thoma, N. H., A. Iakovenko, A. Kalinin, H. Waldmann, R. S. Goody, and K. Alexandrov. Allosteric regulation of substrate binding and product release in geranylgeranyltransferase type Ⅱ. Biochemistry.40:268-274(2001).
[42]Tschantz, W. R., E. S. Furfine, and P. J. Casey. Substrate binding is required for release of product from mammalian protein farnesyltransferase. J. Biol. Chem.272: 9989-9993 (1997).
[43]Park, H-W., S. R. Boduluri, J. F. Moomaw, P. J. Casey, and L. S. Beese. Crystal structure of protein farnesyltransferase at 2.25 A0 resolution. Science.275: 1800-1804(1997).
[44]Brandt W, Brauer L, Gunnewich N, Kufka J, Rausch F, Schulze D, Schulze E, Weber R, Zakharova S, Wessjohann L. Molecular and structural basis of metabolic diversity mediated by prenyldiphosphate converting enzymes. Phytochemistry. 70(15-16):1758-75 (2009).
[45]Kral, A. M., R. E. Diehl, S. J. deSolms, T. M. Williams, N. E. Kohl, and C. A. Omer. Mutational analysis of conserved residues of the beta-subunit of human farnesyl:proteintransferase. J. Biol. Chem.272:27319-27323 (1997).
[46]Clausen, V. A., R. L. Edelstein, and M. D. Distefano. Stereochemical analysis of the reaction catalyzed by human protein geranylgeranyl transferase. Biochemistry.40: 3920-3930(2001).
[47]Seabra MC, Goldstein JL, Sudhof TC, Brown MS. Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys. J Biol Chem.267(20):14497-503 (1992).
[48]Dolence JM, Rozema DB, Poulter CD. Yeast protein farnesyltransferase. Site-directed mutagenesis of conserved residues in the beta-subunit. Biochemistry. 36(30):9246-52(1997).
[49]Wu YW, Goody RS, Abagyan R, Alexandrov K. Structure of the disordered C terminus of Rab7 GTPase induced by binding to the Rab geranylgeranyl transferase catalytic complex reveals the mechanism of Rab prenylation. J Biol Chem. 284(19):13185-92 (2009).
[50]Sasaki, T., A. Kikuchi, S. Araki, Y. Hata, M. Isomura, S. Kuroda, and Y. Takai. Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A, a ras p21-like GTPbinding protein. J. Biol. Chem.265:2333-2337 (1990).
[51]Seabra, M. C. Nucleotide dependence of Rab geranylgeranylation. Rab escort protein interacts preferentially with GDPbound Rab. J. Biol. Chem.271: 14398-14404(1996).
[52]Kloog, Y.& Cox, A. D. Prenyl-binding domains:potential targets for Ras inhibitors and anti-cancer drugs. Semin. Cancer Biol.14,253-261 (2004).
[53]Lurje G, Lenz HJ. EGFR signaling and drug discovery. Oncology.77(6):400-410 (2009).
[54]Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development:EGFR gene and cancer. FEBS J.277(2):301-8(2010).
[55]Daub, H., Specht, K.& Ullrich, A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nature Rev. Drug Discov.3,1001-1110 (2004).
[56]Gschwind, A., Fischer, O. M.& Ullrich, A. The discovery of receptor tyrosine kinases:targets for cancer therapy. Nature Rev. Cancer 4,361-370 (2004).
[57]Lebowitz, P. F., Casey, P. J., Prendergast, G. C.& Thissen, J. A. Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. J. Biol. Chem.272,15591-15594 (1997).
[58]Appels, N. M., Beijnen, J. H.& Schellens, J. H. Development of farnesyl transferase inhibitors:a review. Oncologist 10,565-578 (2005).
[59]Kloog, Y.& Cox, A. D. Prenyl-binding domains:potential targets for Ras inhibitors and anti-cancer drugs. Semin. Cancer Biol.14,253-261 (2004).
[60]Doll, R. J., Kirschmeier, P.& Bishop, W. R. Farnesyltransferase inhibitors as anticancer agents:critical crossroads. Curr. Opin. Drug Discov. Devel.7,478-486 (2004).
[61]Sebti, S. M.& Der, C. J. Searching for the elusive targets of farnesyltransferase inhibitors. Nature Rev. Cancer 3,945-951 (2003).
[62]Caraglia, M., Budillon, A., Tagliaferri, P., Marra, M., Abbruzzese, A.& Caponigro, F. Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms:preclinical and clinical implications. Curr. Drug Targets 6,301-323 (2005).
[63]Morgan, M. A. Combining prenylation inhibitors causes synergistic cytotoxicity, apoptosis and disruption of RAS-to-MAP kinase signalling in multiple myeloma cells. Br. J. Haematol.130,912-925 (2005).
[64]Basso, A. D., Kirschmeier, P.& Bishop, W. R. Lipid post-translational modifications. Farnesyl transferase inhibitors. J. Lipid Res.41,15-31 (2006).
[65]Law, B. K., Norgaard, P.& Moses, H. L. Farnesyltransferase inhibitor induces rapid growth arrest and blocks p70s6k activation by multiple stimuli. J. Biol. Chem.275, 10796-10801 (2000).
[66]Agrawal AG, Somani RR. Farnesyltransferase inhibitor as anticancer agent.Mini Rev Med Chem.9(6):638-52(2009).
[67]Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D. Phase Ⅲ trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J. Clin. Oncol.22, 1430-1438 (2004).
[68]Rao S, Cunningham D, de Gramont A, Scheithauer W, Smakal M, Humblet Y, Kourteva G, Iveson T, Andre T, Dostalova J, Illes A, Belly R, Perez-Ruixo JJ, Park YC, Palmer PA. Phase Ⅲ double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer.J.Clin. Oncol.22,3950-3957 (2004).
[69]Fouladi M, Nicholson HS, Zhou T, Laningham F, Helton KJ, Holmes E, Cohen K, Speights RA, Wright J, Pollack IF; Children's Oncology Group. A phase Ⅱ study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma:a Children's Oncology Group study. Cancer.110(11):2535-41(2007).
[70]Dalenc F, Doisneau-Sixou SF, Allal BC, Marsili S, Lauwers-Cances V, Chaoui K, Schiltz O, Monsarrat B, Filleron T, Renee N, Malissein E, Meunier E, Favre G, Roche H. Tipifarnib plus tamoxifen in tamoxifen-resistant metastatic breast cancer:a negative phase Ⅱ and screening of potential therapeutic markers by proteomic analysis. Clin Cancer Res.16(4):1264-71 (2010).
[71]Ravoet C, Mineur P, Robin V, Debusscher L, Bosly A, Andre M, El Housni H, Soree A, Bron D, Martiat P. Farnesyl transferase inhibitor (lonafarnib) in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia:a phase Ⅱ study.Ann Hematol.87(11):881-885 (2008).
[72]Dinsmore CJ, Bell IM. Inhibitors of farnesyltransferase and geranylgeranyltransferase-I for antitumor therapy:substrate-based design, conformational constraint and biological activity. Curr Top Med Chem. 3(10):1075-1093 (2003).
[73]Chiba Y, Sato S, Misawa M. GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. Int J Immunopathol Pharmacol.22(4):929-35 (2009).
[74]Huang XK, Meyer P, Li B, Raza A, Preisler HD. The effects of the farnesyl
transferase inhibitor FTI L-778,123 on normal, myelodysplastic, and myeloid leukemia bone marrow progenitor proliferation in vitro.Leuk Lymphoma. 44(1):157-164 (2003).
[75]Caraglia M, Budillon A, Tagliaferri P, Marra M, Abbruzzese A, Caponigro F. Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms:preclinical and clinical implications.Curr Drug Targets.6(3):301-323 (2005).
[76]Maiello MR, D'Alessio A, De Luca A, Carotenuto A, Rachiglio AM, Napolitano M, Cito L, Guzzo A, Normanno N. AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib.Breast Cancer Res Treat.102(3):275-282 (2007).
[77]Appels NM, Bolijn MJ, van Eijndhoven MA, Stephens TC, Beijnen JH, Schellens JH. Characterization of the in vitro activity of AZD3409, a novel prenyl transferase inhibitor. Cancer Chemother Pharmacol.2010 Mar 13.
[78]Appels NM, Bolijn MJ, Chan K, Stephens TC, Hoctin-Boes G, Middleton M, Beijnen JH, de Bono JS, Harris AL, Schellens JH. Phase I pharmacokinetic and pharmacodynamic study of the prenyl transferase inhibitor AZD3409 in patients with advanced cancer. Br J Cancer.98(12):1951-1958 (2008).
[79]Lu Q, Harrington EO, Newton J, Jankowich M, Rounds S. Inhibition of ICMT induces endothelial cell apoptosis through GRP94. Am J Respir Cell Mol Biol. 37(1):20-30(2007).
[80]Baron RA, Peterson YK, Otto JC, Rudolph J, Casey PJ. Time-dependent inhibition of isoprenylcysteine carboxyl methyltransferase by indole-based small molecules.Biochemistry.46(2):554-560 (2007).
[81]Winter-Vann AM, Baron RA, Wong W, dela Cruz J, York JD, Gooden DM, Bergo MO, Young SG, Toone EJ, Casey PJ. A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells.Proc Natl Acad Sci USA.102(12):4336-41 (2005).
[82]Donelson JL, Hodges HB, Macdougall DD, Henriksen BS, Hrycyna CA, Gibbs RA. Amide-substituted farnesylcysteine analogs as inhibitors of human isoprenylcysteine carboxyl methyltransferase.Bioorg Med Chem Lett.16(16):4420-3 (2006).
[83]Wang M, Tan W, Zhou J, Leow J, Go M, Lee HS, Casey PJ. A small molecule inhibitor of isoprenylcysteine carboxymethyltransferase induces autophagic cell death in PC3 prostate cancer cells.J Biol Chem.283(27):18678-84 (2008).
[84]Lu Q, Harrington EO, Hai CM, Newton J, Garber M, Hirase T, Rounds S. Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis. Mol. Biol. Cell 14,848-857 (2003).
[85]Fehrenbacher N, Bar-Sagi D, Philips M. Ras/MAPK signaling from endomembranes. Mol Oncol.3(4):297-307 (2009).
[86]Peterson, Y. K., Kelly, P., Weinbaum, C. A.&Casey, P. J. A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity. J. Biol. Chem.281,12445-12450(2006).
[87]Fritz G. Targeting the mevalonate pathway for improved anticancer therapy. Curr Cancer Drug Targets.9(5):626-38 (2009).