宫颈癌组织中DNA修复基因06-甲基鸟嘌呤-DNA甲基转移酶启动子区过甲基化研究  

Promoter hypermethylation of DNA repair gene 06-Methylguanine DNA methyltransferase in cervical carcinoma.

作　　者：高艳萍[1] 王泽华[1] 李敏[1] 张颖颖[1] 王翰[1] 贺小红[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022

出　　处：《现代妇产科进展》2007年第8期569-572,共4页Progress in Obstetrics and Gynecology

摘　　要：目的：研究宫颈癌中06-甲基鸟嘌呤-DNA甲基转移酶（06-Methylguanine-DNA Methyltransferase，MGMT）基因甲基化状态及其mRNA的表达，探讨MGMT基因甲基化与其基因表达缺陷的关系。方法：用甲基化特异性PCR（MSP）、半定量逆转录聚合酶链反应（RT-PCR）法检测4株宫颈癌细胞、15例正常宫颈组织、20例宫颈上皮内瘤变及38例宫颈浸润癌组织中MGMT基因启动子区过甲基化状态及其mRNA的表达，同时分析MGMT基因甲基化与宫颈癌病理分级、临床分期及淋巴转移之间的关系。结果：4株宫颈癌细胞、正常宫颈组织及CINⅠ组织中无MGMT基因甲基化，MGMT甲基化在CINⅡ～CINⅢ组织中占27％，浸润性宫颈癌中占31％。MGMT基因甲基化在不同的病理分级（P=0．263）和临床分期（P=0．342）中差异无显著性，在有无盆腔淋巴结转移上，差异有显著性（Х^2=7．785，P=0．005）。所有MGMT甲基化的癌组织及CIN组织均无MGMT mRNA表达，而所有非MGMT甲基化癌组织、CIN组织和正常宫颈组织均有MGMT mRNA表达。结论：宫颈癌中MGMT基因启动子区异常甲基化是导致此基因表达缺陷的主要原因。Objective： To study the 06-Methylguanine-DNA Methyltransferase （ MGMT） gene methylation and its mRNA expression in cervical carcinoma and to analyze the relation between this alteration and the promoter methylation of MGMT DNA. Methods： Methylation specific PCR （MSP） and reverse transcription polymerase chain reaction （RT-PCR） were used to detect the hypermethylation state in MGMT gene promoter region and expression of MGMT gene in 4 types of cervical cancer cell lines, 15 cases of normal cervical tissues,20 cases of cevical intraepithehal neoplasia and 38 cases of cevical invasive carcinomatous tissues. The relationship between MGMT gene methylation and the pathological grade, clinical stage and lymphoid metastasis of the cervical cancer was analysed. Results： There were no MGMT gene methylation in 4 types of cervical cancer cell lines, normal cervical tissues and CINⅠ tissues. The MGMT gene methylation could be detected in CINⅡ-CINⅢ tissues and cervical invasive carcinoma,27% and 31% respectively. There was no significant difference of MGMT gene methylation in different clinical pathological types （ P = 0. 263 ） and clinic stages （ P = 0.342 ）. MGMT gene methylation was significantly related to between pelvic lymphatic metastases（ Х^2 = 7.785. P = 0. 005 ）. There was no expression of MGMT mRNA in the methylated cancer tissues,whereas expression of MGMT mRNA could be detected in the unmethylated cancer tissues,CIN tissues and normal cervical tissues. Conclusion：Aberrant methylation in promotor regions of MGMT gene may be an important mechanism for the loss of expression of MGMT gene.

关 键 词：06-甲基鸟嘌呤-DNA甲基转移酶 甲基化 宫颈肿瘤 

分 类 号：R737.33[医药卫生—肿瘤]