胶质瘤细胞株中ERCC1、ERCC2基因启动子区CpG岛的甲基化分析  

Methylation Status in the ERCC1 and ERCC2 Promoter in Glioma Cell Lines

作　　者：陈华云[1] 张俊英[1] 陈忠平[1] 

机构地区：[1]华南肿瘤学国家重点实验室中山大学肿瘤防治中心神经外科/神经肿瘤科,广东广州510060

出　　处：《中国神经肿瘤杂志》2005年第4期243-247,共5页Chinese Journal of Neuro-Oncology

基　　金：国家自然科学基金(No.30271329);华南肿瘤学国家重点实验室基金(No.985-Ⅱ)

摘　　要：背景与目的:NER是DNA修复系统中一个由多种蛋白组成的复杂网状系统,其中作为主要组成成分的ERCC1的高表达同DDP化疗耐受相关,ERCC2的高表达同烷基药物化疗耐受相关。研究已经发现某些基因启动子区CpG岛的甲基化会导致基因的表达沉默,对化疗反应有指示作用。本文探讨ERCC1和ERCC2启动子区的甲基化状态和耐药的关系。方法:应用亚硫酸氢钠处理基因组DNA后PCR和测序,我们分析了5个具有不同药敏特征的胶质瘤细胞株ERCC1和ERCC2的甲基化状态。人脑胶质瘤细胞株UW28,MGR1,MGR2,SF767和T98G对DDP和MeCCNU的敏感性采用MTT法检测。结果:在DDP敏感的细胞株中发现ERCC1基因启动子区上游4.9kb处存在甲基化的CpG岛。而在5个对BCNU耐药的细胞株中ERCC2的启动子区的CpG岛均呈去甲基化状态。结论:ERCC1和ERCC2畸变的甲基化状态与胶质瘤细胞株对化疗药的敏感性有关。BACKGROUND ＆ OBJECTIVE： NER pathway is a complex network of DNA-repair system which involved with many proteins. In this system, ERCCI over expression is known to he related with platinum-resistauce while ERCC2 over expression is related to BCNU-resistauce. It has heen proved that methylation of the CpG; island in the promoter region is associated with silencing of the genes. In this study we analysis the relationship of methylation status in the ERCC1 and ERCC2 promoter and auti-vaneer drug resistance in glioma cell lines. METHODS： Using bisulphate sequeneing, we have identified hypennethylation in the promoter region of ERCC1 and ERCC2 in five gliomas cell lines.UW28、MGR1、MGR2、SF767 and T98G.The sensitivity of the cell lines to anti-cancer drug MeCCNU and DDP were determined by MTT assay.RESULTS：The methylated CpG is land in the 4.9kb region of ERCC1 gene promoter upstream in the platinum-sensitive cell lines has been recognized and the putative CpG island of ERCC2 promoter showed the ummethylated status in all five BCNU-resistant cell lines.CONCLUSION：Our data indicate that aberrant methylation status of ERCC1 and ERCC2 were associated with chemoensitivity in gliomas cell lines.

关 键 词：甲基化 表现遗传学 胶质瘤 细胞株 ERCC1 ERCC2 基因启动子 

分 类 号：R739.41[医药卫生—肿瘤]