错配修复基因启动子甲基化对食管癌发生的作用  

Effects of hMLH1 promoter methylation on esophageal carcinoma

作　　者：张军航[1] 刘芙蓉[1] 马琳[2] 玉寒冰[3] 张林[4] 

机构地区：[1]中国医科大学卫生部细胞生物学重点实验室,沈阳110001 [2]中国医科大学附属第二医院妇产科 [3]辽宁省肿瘤医院胸外科 [4]中国医科大学附属第一医院胸外科

出　　处：《中国公共卫生》2005年第7期780-781,共2页Chinese Journal of Public Health

基　　金：国家自然科学基金资助项目(30100104);辽宁省博士启动基金资助课题(2001102037);2000年度辽宁省重点科技项目(00225003)

摘　　要：目的探讨食管癌组织中错配修复基因1(hMLH1)启动子区甲基化状态及与食管癌发生、发展的关系。方法应用甲基化特异性PCR和免疫组织化学链霉菌抗亲生物素蛋白-过氧化物酶连接法(S-P法),检测92例人食管癌组织中hMLH1启动子甲基化状态及蛋白表达。结果92例食管癌组织中hMLH1基因启动子区甲基化有30例,占32.6%。HMLH1基因启动子区甲基化与食管癌的临床病理无明显相关性;hMLH1基因蛋白表达阳性率为76.1%;hMLH1基因蛋白表达阴性的22例病例中,17例发生了甲基化(77.6%);而70例hMLH1基因蛋白表达阳性者中,只有13例发生甲基化(18.6%)。结论食管癌组织中hMLH1基因启动子区甲基化与hMLH1基因蛋白表达缺失密切相关,是导致其错配修复功能缺陷的重要原因之一,hMLH1基因启动子区甲基化可能在食管癌的发生和发展过程中发挥重要作用。Objective To study methylation of the hMLH1 promoter and its correlation with esophageal carcinoma.Methods Methylation of the hMLH1 promoter was examined by Methylation Specific PCR(MSP) in 92 esophageal carcinomas and the expression patterns of hMLH1 gene was detected by immunohistochemistry method using multiclonal antibody to hMLH1 protein.Results The incidence of the hMLH1 promoter methylation was 32.6%(30/92).Methylation did not correlate with clinicopathological characteristics of esophageal carcinoma.17 of 22(77.6%) hMLH1 protein negative tumors exhibited prominent methylation,compared with 13 of 70(18.6%) tumors with positive expression of hMLH1 protein.Conclusion hMLH1 methylation was associated with the absence of hMLH1 expression and might be the underlying cause of mismatch repair gene defects in esophageal carcinoma.Promoter methylation of the hMLH1 involved in tumorigenic process of esophageal carcinoma.

关 键 词：食管癌 HMLH1基因 启动子甲基化 

分 类 号：R735.1[医药卫生—肿瘤]