Apaf-1在甲状腺乳头状癌中的表达及意义
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摘要
目的:探讨凋亡蛋白酶活化因子1(Apaf-1)在甲状腺乳头状癌(PTC)中的m RNA与蛋白表达及其与细胞增殖的关系。方法:分别采用real-time PCR、Western blot及免疫组化法检测并比较甲状腺乳头状癌和癌旁组织中Apaf-1的m RNA及蛋白表达情况,并分析其表达水平与PTC临床病理学特征的关系;通过下调CGTHW-3细胞中Apaf-1表达量,验证Apaf-1对细胞增殖的影响。结果:在PTC组织中,Apaf-1的m RNA和蛋白表达量均显著低于癌旁组织(P <0. 05);下调Apaf-1表达增强了CGTHW-3细胞的增殖活性(P <0. 05)。结论:Apaf-1在PTC中低表达,抑制其表达可增强CGTHW-3细胞的增殖能力。Apaf-1在甲状腺乳头状癌中可能发挥抑癌作用。
AIM: To investigate the m RNA and protein expression of apoptotic protease-activating factor 1( Apaf-1) in papillary thyroid carcinoma( PTC) and its relationship with cell proliferation. METHODS: The methods of real-time PCR,Western blot and immunohistochemistry were used to detect the m RNA and protein expression of Apaf-1 in PTC and tumor-adjacent tissues. The relationship between Apaf-1 expression and clinicopathological characteristics was analyzed. The effect of Apaf-1 on cell proliferation was verified by down-regulating the expression of Apaf-1 in CGTHW-3cells. RESULTS: The m RNA and protein expression levels of Apaf-1 in the PTC tissue were significantly lower than those in the tumor-adjacent tissue( P < 0. 05). Down-regulation of Apaf-1 expression enhanced the proliferation of CGTHW-3cells( P < 0. 05). CONCLUSION: The expression of Apaf-1 is low in PTC,and inhibition of its expression enhances the proliferation of CGTHW-3 cells. Apaf-1 may play a tumor suppressor role in PTC.
AIM: To investigate the m RNA and protein expression of apoptotic protease-activating factor 1( Apaf-1) in papillary thyroid carcinoma( PTC) and its relationship with cell proliferation. METHODS: The methods of real-time PCR,Western blot and immunohistochemistry were used to detect the m RNA and protein expression of Apaf-1 in PTC and tumor-adjacent tissues. The relationship between Apaf-1 expression and clinicopathological characteristics was analyzed. The effect of Apaf-1 on cell proliferation was verified by down-regulating the expression of Apaf-1 in CGTHW-3cells. RESULTS: The m RNA and protein expression levels of Apaf-1 in the PTC tissue were significantly lower than those in the tumor-adjacent tissue( P < 0. 05). Down-regulation of Apaf-1 expression enhanced the proliferation of CGTHW-3cells( P < 0. 05). CONCLUSION: The expression of Apaf-1 is low in PTC,and inhibition of its expression enhances the proliferation of CGTHW-3 cells. Apaf-1 may play a tumor suppressor role in PTC.
引文
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[17]Gogada R,Amadori M,Zhang H,et al.Curcumin induces Apaf-1-dependent,p21-mediated caspase activation and apoptosis[J].Cell Cycle,2011,10(23):4128-4137.
[18]Jung J,Kim HY,Maeng J,et al.Interaction of translationally controlled tumor protein with Apaf-1 is involved in the development of chemoresistance in He La cells[J].BMC Cancer,2014,14:165.
[19]Zhang XW,Liu N,Chen S,et al.Upregulation of micro RNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma[J].Oncol Lett,2015,10(1):410-416.
[2]杨雷,郑荣寿,王宁,等.2013年中国甲状腺癌发病与死亡情况[J].中华肿瘤杂志,2017,39(11):862-867.
[3]Siegel RL,Miller KD,Jemal A,et al.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[4]杨晶金,姚军,沈峰清,等.Notch-1信号通路与甲状腺乳头状癌的关系[J].中国细胞生物学学报,2012,34(2):120-126.
[5]沈沁彦,伍慧慧,梁津逍,等.SUMO4在甲状腺乳头状癌中的表达及临床意义[J].中国病理生理杂志,2015,31(8):1422-1426.
[6]Mustika R,Budiyanto A,Nishigori C,et al.Decreased expression of Apaf-1 with progression of melanoma[J].Pigment Cell Res,2005,18(1):59-52.
[7]Choi S,Lew KL,Xiao H,et al.D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1[J].Carcinogenesis,2007,28(1):151-162.
[8]Carcangiu ML,Chambers JT,Voynick IM,et al.Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma.Part I:Clinical and histologic correlation[J].Am J Clin Pathol,1990,94(3):247-254.
[9]Zou H,Henzel WJ,Liu X,et al.Apaf-1,a human protein homologous to C.elegans CED-4,participates in cytochrome c-dependent activation of caspase-3[J].Cell,1997,90(3):405-413.
[10]Christoph F,Kempkensteffen C,Weikert S,et al.Methylation of tumour suppressor genes APAF-1 and DAPK-1and in vitro effects of demethylating agents in bladder and kidney cancer[J].Br J Cancer,2006,95(12):1701-1707.
[11]Fujimoto A,Takeuchi H,Taback B,et al.Allelic imbalance of 12q22-23 associated with APAF-1 locus correlates with poor disease outcome in cutaneous melanoma[J].Cancer Res,2004,64(6):2245-2250.
[12]Watanabe T,Hirota Y,Arakawa Y,et al.Frequent LOHat chromosome 12q22-23 and Apaf-1 inactivation in glioblastoma[J].Brain Pathol,2003,13(4):431-439.
[13]Umetani N,Fujimoto A,Takeuchi H,et al.Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma[J].Oncogene,2004,23(50):8292-8300.
[14]Robles AI,Bemmels NA,Foraker AB,et al.APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis[J].Cancer Res,2001,61(18):6660-6664.
[15]Wallace DM,Cotter TG.Histone deacetylase activity in conjunction with E2F-1 and p53 regulates Apaf-1 expression in 661W cells and the retina[J].J Neurosci Res,2009,87(4):887-905.
[16]Choi S,Singh SV.Bax and Bak are required for apoptosis induction by sulforaphane,a cruciferous vegetable-derived cancer chemopreventive agent[J].Cancer Res,2005,65(5):2035-2043.
[17]Gogada R,Amadori M,Zhang H,et al.Curcumin induces Apaf-1-dependent,p21-mediated caspase activation and apoptosis[J].Cell Cycle,2011,10(23):4128-4137.
[18]Jung J,Kim HY,Maeng J,et al.Interaction of translationally controlled tumor protein with Apaf-1 is involved in the development of chemoresistance in He La cells[J].BMC Cancer,2014,14:165.
[19]Zhang XW,Liu N,Chen S,et al.Upregulation of micro RNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma[J].Oncol Lett,2015,10(1):410-416.