膀胱移行细胞癌微卫星不稳定性表达及机理探讨  

Microsatellite instability in urine sediments from patients with transitional cell carcinoma of bladder and its mechanisms

作　　者：俞莉章[1] 唐东起[1] 丁义[1] 刘漓波[1] 郭应禄[1] 

机构地区：[1]北京大学第一医院泌尿研究所,100034

出　　处：《中华外科杂志》2001年第1期60-63,共4页Chinese Journal of Surgery

基　　金：卫生部基金!资助项目 (9812 5 6 )

摘　　要：目的　探讨微卫星不稳定性在膀胱移行细胞癌的表达及其作用机制。　方法　用PCR方法分析 35例膀胱移行细胞癌尿沉渣标本中微卫星不稳定性表达 ;用RT PCR方法监测 5种人类错配修复基因在膀胱癌细胞系mRNA转录水平的表达 ;用PCR方法检测膀胱癌细胞系BIU 87中错配修复基因hMLH1的启动子区域出现异常甲基化。　结果　 35例膀胱癌患者尿沉渣中 ,有 31例(88 6 % )可检出微卫星不稳定性表现 ;5种人的错配修复基因在BIU 87膀胱癌细胞系中有hMLH1和hMSH2表达缺失 ,而在正常近曲小管细胞系中都有表达 ;BIU 87细胞错配修复基因hMLH1的启动子区域出现异常甲基化 ,应用去甲基化剂处理后可检测到hMLH1的启动子区域的表达 ,再次去除去甲基化剂后又不能检测hMLH1的启动子区域。　结论　微卫星不稳定性与错配修复基因表达有关。甲基化对膀胱癌细胞系BIU 87错配修复基因hMLH1的表达具有调控作用。Objective To investigate the expression of microsatellite instability(MSI) in the transitional cell carcinoma (TCC) of bladder and its mechanisms. [WT5”HZ]Methods[WT5”BZ] Urine samples from 35 patients with TCC were analyzed for MSI by PCR. The expression of mRNA by RT PCR of 5 human mismatch repair(MMR) genes in bladder tumor cell line was evaluated. PCR method was used to detect the methylation of MMR gene promoter region. [WT5”HZ]Results[WT5”BZ] Microsatellite instability was detected in the urine sediments of 31 of the 35 patients (88 6%). There was no expression of MMR genes, hMLH1 and hMSH2 in BIU 87, but all 5 MMR genes were expressed in normal cell line. The cytosine methylation of hMLH1 gene in promoter region was found in bladder tumor cell line BIU 87. But it could be turned on or off by exposure in 5 azacytidine or without. [WT5”HZ]Conclusion[WT5”BZ] There is the relationship between MSI and the expression of MMR gene. The expression of MMR gene hMLH1 in BIU 87 is controlled by cytosine methylation.

关 键 词：基因表达 甲基化 膀胱移行细胞癌 微卫星不稳定性 

分 类 号：R737.14[医药卫生—肿瘤]