GSTM1基因多态性及启动子甲基化在结肠癌细胞系中的研究  

GSTM1 genetic polymorphisms and promoter methylation in colon cancer cell lines

作　　者：田筱青[1] 孙丹凤[1] 房静远[1] 

机构地区：[1]上海交通大学医学院附属仁济医院消化科,上海市消化疾病研究所,上海200001

出　　处：《西安交通大学学报（医学版）》2014年第1期56-58,93,共4页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的研究参与内毒物代谢的重要酶谷胱甘肽-S-转移酶M1(glutathione-s-transferase M1,GSTM1)在结肠癌细胞系中的基因表达状况与其遗传基因型及启动子甲基化的关系。方法采用多重PCR方法检测GSTM1基因型,甲基化特异PCR(MSP)方法检测GSTM1基因启动子甲基化状态;用5-aza-dC处理结肠癌细胞系,RT-PCR方法检测GSTM1基因转录水平。结果结肠癌细胞系HT29、SW480、SW1116为GSTM1非空白基因型,而HCT116、Lovo、Colo结肠癌细胞系为GSTM1空白基因型。MSP检测发现SW1116细胞中GSTM1基因主要呈非甲基化状态,其他5个细胞系中呈甲基化状态,而且基因表达缺失。经5-aza-dC处理后,HT29和SW480细胞的GSTM1基因表达复活,而HCT116、Lovo、Colo细胞中GSTM1仍无扩增。结论 GSTM1基因转录受到遗传基因型和表观遗传启动子甲基化双重调控。Objective To explore the expression of glutathione-s-transferase M1 （GSTM1）, an important enzyme participating in endotoxin metabolism, in colon cancer cell lines and the association of GSTM1 with its genotypes and promoter methylation. Methods The genotypes of GSTM1 were detected with multiple polymerase chain reaction （PCR） technique. GSTM1 methylation in the promoter was detected in 6 colon cancer cell lines by methylation-specific （MSP） PCR. GSTM1 expression in 6 colon cancer cell lines was also assayed by RT-PCR after 5-aza-dC treatment. Results GSTMl-positive genotypes were detected in HT29, SW480 and SWl116 cells. GSTMI-null genotypes were detected in HCTlI6, Lovo and Colo cells. GSTMI gene promoter was unmethylated in SWl116 cell. GSTM1 promoter methylation was detected in the other 5 cell lines by MSP, and GSTM1 expression was reactivated in HT29 and SW480 cells after 5-aza-dC treatment. Conclusion GSTM1 gene transcription is controlled by both the genetic polymorphisms and epigenetic promoter methylation.

关 键 词：结肠癌 谷胱甘肽-S-转移酶M1(GSTM1) 基因多态性 甲基化 甲基化特异PCR 

分 类 号：R735.3[医药卫生—肿瘤]