探讨转录因子SRF在人食管鳞癌中的表达
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摘要
目的探讨转录因子serum response factor ( SRF)在人食管鳞癌中的表达以及它和临床病理各参数的关系。
方法应用高通量的组织芯片以及免疫组化技术,分析了115例食管鳞癌患者的SRF的表达情况,在其蛋白质水平上,研究SRF在食管鳞癌组织和配对的手术切缘黏膜组织的差异表达量,探讨该转录因子在食管鳞癌中的表达与临床病理各变量之间的关系。
结果SRF在食管癌组织中的表达比在手术切缘黏膜组织中的表达显著升高,两者表达差异具有显著相关性(P<0.01);食管鳞癌中SRF的过表达与肿瘤的分化程度、浸润深度及淋巴结转移无显著相关性(P>0.05)。
结论转录因子SRF在食管癌的发生中可能具有重要作用,具体机理及其表达与患者的预后是否相关有待进一步研究。
AIM: To investigate the expression pattern of serum response factor(SRF)in human esophageal squamous cell carcinoma (ESCC) and to analyze its relationship with clinicopathologic parameters.
METHODS: The protein expression of SRF in human esophageal cancer tissues and their corresponding normal mucosa was detected immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation with clinical characteristics was evaluated and analyzed by Chi square test and Kruskal Wallis text. All statistical analyses were performed by SPSS version 11.0.
RESULTS: The increased expression of transcription factor SRF was 62.6% (72/115) in ESCC tissues compared with their matched normal esophageal epithelium. However, the expression of SRF did not show any obvious correlation with age, gender, histological grade, lymph node metastasis and depth of invasion.
CONCLUSION: Increased expression of transcription factor SRF may play an important role in esophageal carcinogenesis.
方法应用高通量的组织芯片以及免疫组化技术,分析了115例食管鳞癌患者的SRF的表达情况,在其蛋白质水平上,研究SRF在食管鳞癌组织和配对的手术切缘黏膜组织的差异表达量,探讨该转录因子在食管鳞癌中的表达与临床病理各变量之间的关系。
结果SRF在食管癌组织中的表达比在手术切缘黏膜组织中的表达显著升高,两者表达差异具有显著相关性(P<0.01);食管鳞癌中SRF的过表达与肿瘤的分化程度、浸润深度及淋巴结转移无显著相关性(P>0.05)。
结论转录因子SRF在食管癌的发生中可能具有重要作用,具体机理及其表达与患者的预后是否相关有待进一步研究。
AIM: To investigate the expression pattern of serum response factor(SRF)in human esophageal squamous cell carcinoma (ESCC) and to analyze its relationship with clinicopathologic parameters.
METHODS: The protein expression of SRF in human esophageal cancer tissues and their corresponding normal mucosa was detected immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation with clinical characteristics was evaluated and analyzed by Chi square test and Kruskal Wallis text. All statistical analyses were performed by SPSS version 11.0.
RESULTS: The increased expression of transcription factor SRF was 62.6% (72/115) in ESCC tissues compared with their matched normal esophageal epithelium. However, the expression of SRF did not show any obvious correlation with age, gender, histological grade, lymph node metastasis and depth of invasion.
CONCLUSION: Increased expression of transcription factor SRF may play an important role in esophageal carcinogenesis.
引文
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2.Ruggieri M, Tosato F, De Rocco K, et al. Epidemiological aspects of esophageal cancer. Recenti Prog Med. 1981; 70(5): 545-556.
3. Montesano R, Hollstein M, Hainaut P, et al. Genetic alterations in esophageal cancer and their relevance to etiology and pathogenesis: a review. Int J Cancer. 1996; 69(3): 225-235.
4. Oka M, Yamamoto K, Takahashi M, et al. Relationship between serum levels of interleukin 6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res. 1996; 56(12): 2776-2780.
5. Hu N, Dawsey SM, Wu M, et al. Familial aggregation of oesophageal cancer in Yangcheng County, Shanxi Province, China. Int J Epidemiol. 1992; 21(5): 877-882.
6. Hu N, Dawsey SM, Wu M, et al. Family history of oesophageal cancer in Shanxi Province, China. Eur J Cancer. 1991; 27(10): 1336.
7. Morita M, Kuwano H, Nakashima T, et al. Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract. Int J Cancer. 1998; 76(4): 468-471.
8. Zhang W, Bailey-Wilson JE, Li W, et al. Segregation analysis of esophageal cancer in a moderately high-incidence area of northern China. Am J Hum Genet. 2000; 67(1): 110-119.
9. Li JY, Taylor PR, Li B, et al. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J Natl Cancer Inst. 1993; 85(18): 1492-1498.
10. Lu SH, Ohshima H, Fu HM, et al. Urinary excretion of N-nitrosamino acids andnitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C. Cancer Res. 1986; 46(3): 1485-1491.
11. Terry P, Lagergren J, Ye W, et al. Antioxidants and cancers of the esophagus and gastric cardia. Int J Cancer. 2000; 87(5): 750-754.
12. Treisman R, Marais R, Wynne J. Spatial flexibility in ternary complexes between SRF and its accessory proteins. EMBO J 1992 Dec; 11(12): 4631-4640.
13. Norman C, Runswick M, Pollock R, et al. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell 1988 Dec; 55(6): 989-1003.
14. Treisman R. Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J 1987 Sep; 6(9): 2711-2717.
15. Gilman M, Wilson R, Weinberg R. Multiple protein-binding sites in the 5'-flanking region regulate c-fos expression. Mol Cell Biol 1986 Dec; 6(12): 4305-4316.
16. Minty A, Kedes L. Upstream regions of the human cardiac actin gene that modulate its transcription in muscle cells: presence of an evolutionarily conserved repeated motif. Mol Cell Biol 1986 Jun; 6(6): 2125-2136.
17. Gineitis D, Treisman R. Differential usage of signal transduction pathways defines two types of serum response factor target gene. J Biol Chem 2001 Jul; 276(27): 24531-24539.
18. Iyer V, Eisen M, Ross D, et al. The transcriptional program in the response of human fibroblasts to serum. Science 1999 Jan; 283(5398): 83-87.
19. Chang J, Wei L, Otani T, et al. Inhibitory cardiac transcription factor, SRF-N, is generated by caspase 3 cleavage in human heart failure and attenuated by ventricular unloading. Circulation 2003 Jul; 108(4): 407-413.
20. Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998; 4(7): 844-847.
21. Shergill IS, Rao AR, Anjum FH, et al. Tissue microarrays and their relevance to the urologist. J Urol. 2006; 175(1): 19-26.
22. Gomaa W, Ke Y, Fujii H, et al. Tissue microarray of head and neck squamous carcinoma: validation of the methodology for the study of cutaneous fatty acid-binding protein, vascular endothelial growth factor, involucrin and Ki-67. Virchows Arch. 2005; 447(4): 701-709.
23. Sarbia M, Loberg C, Wolter M, et al. Expression of Bcl-2 and amplification of c-myc are frequent in basaloid squamous cell carcinomas of the esophagus. Am J Pathol. 1999; 155(4): 1027-1032.
24. Hao XP, Pretlow TG, Rao JS, et al. Beta-catenin expression is altered in human colonic aberrant crypt foci. Cancer Res. 2001; 61(22): 8085-8088.
25. Lin YC, Wu MY, Li DR, et al. Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma . World J Gastroenterol. 2004; 10(22): 3235-3239.
26. Belaguli N, Schildmeyer L, Schwartz R. Organization and myogenic restricted expression of the murine serum response factor gene. A role for autoregulation. J Biol Chem 1997 Jul; 272(29): 18222-18231.
27. McDonough P, Hanford D, Sprenkle A, et al. Collaborative roles for c-Jun N-terminal kinase, c-Jun, serum response factor, and Sp1 in calcium-regulated myocardial gene expression. J Biol Chem 1997 Sep; 272(38): 24046-24053.
28. Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev 1994 Feb; 4(1): 96-101.
29. Johansen F, Prywes R. Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor. Mol Cell Biol 1994 Sep; 14(9): 5920-5928.
30. Ma Z, Morris S, Valentine V, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001 Jul; 28(3):220-221.
31. Sasazuki T, Sawada T, Sakon S, et al. Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death. J Biol Chem 2002 Aug; 277(32): 28853-28860.
32. Cen B, Selvaraj A, Burgess R, et al. Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes. Mol Cell Biol 2003 Sep; 23(18): 6597-6608.
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