肝癌组织中雌激素受体基因启动子甲基化及临床研究  

Promoter methylation of ER gene and clinicopathologic features in hepatocellular carcinoma

作　　者：张长松[1] 李克[1] 李正友[2] 贾凤歧[3] 李蓉[3] 吴孟超[3] 卫立辛[3] 

机构地区：[1]汕头大学医学院分子流行病学教研室,广东汕头515041 [2]山东师范大学生命科学学院,山东济南250014 [3]第二军医大学东方肝胆外科医院肿瘤免疫与基因治疗中心,上海200438

出　　处：《中华肿瘤防治杂志》2007年第4期245-248,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30471994);上海市科委基础研究重大项目(04DZ14006);上海市科委浦江人才计划项目(05PJ14010)

摘　　要：目的:研究原发性肝细胞癌(hepa-tocellular carcinoma,HCC)组织中ER基因启动子甲基化修饰与临床病理特征间的关系,同时观察5-杂氮胞苷对ERmRNA表达的影响。方法:分别采用MSP和RT-PCR方法检测30例HCC及癌旁组织中ER基因启动子甲基化修饰状况及ERmRNA的表达状况,并用5-杂氮胞苷处理肝癌细胞系SMMC-7721和HepG2。结果:30例HCC组织中ER启动子甲基化修饰阳性率为60·0%(18/30),而30例癌旁组织中ER基因启动子甲基化修饰阳性率为30·0%(9/30),两者差异有统计学意义,χ2=5·46,P=0·037。30例HCC组织中ERmRNA阳性表达12例(40·0%),其中甲基化组织和未甲基化组织中ERmRNA表达率分别为22·2%和66·7%。ER启动子甲基化修饰与mRNA表达呈负性相关,χ2=5·93,P=0·024。同时,ER启动子区甲基化修饰与肝癌患者血清AFP含量增高呈正相关,χ2=12·13,P=0·001。细胞培养结果提示低浓度的5-杂氮胞苷可诱导肝癌细胞系ERmRNA重新表达。结论:肝癌组织中ER启动子甲基化修饰是个频繁事件,因此沉默ER基因的表达有可能促进肝癌的发展。OBJECTIVE： To investigate the relationship between promoter of ER methylation and ER mRNA expression and clinicopathologic features in hepatocellular carcinoma （HCC）. And to observe the effects of 5-aza-2-deoxycytidine （5-aza-dc） in regulating ER mRNA expression. METHODS： Promoter methylation of the ER gene was determined by methylation-specific PCR （MSP） in HCC and non-tumor cases. And the expression of ER mRNA was investigated by RT-PCR. Two hepatic cancer cell lines SMMC-7721 and HepG2 were treated with DNA methyltransferase inhibitor, 5-aza-dc. RESULTS： Promoter of the ER gene was methylated in 60.0% （18/30）of HCC and 30.0%（9/30）of non-tumor tissues, respectively. Statistically significant association was found between the status of aberrant methylation in HCC and non-tumor case, X^2 = 5. 455, P = 0. 037. The expression of ER mRNA was 40.0% （12/30） in HCC, while the expression of ER mRNA was 22.2% and 66.7% in methylated HCC cases and unmethylated HCC cases, respectively. An inverse correlation was found between promoter methylation and ER mRNA transcript levels in HCC, X^2 =5.93,P=0. 024. Meanwhile, there was a significant association between methylation of the ER gene and serum AFP level, X^2=12.13,P=0.001. The study shows that low micromolar concentrations of 5-aza-dc induce the ER mRNA expression of in HCC cancer lines. CONCLUSION： Promoter methylation of ER gene is a frequent event in HCC and may contribute to pathogenesis of HCC through silencing ER mRNA expression.

关 键 词：癌 肝细胞/代谢 受体 雌激素/代谢 DNA甲基化 脱氧胞苷/药理学 

分 类 号：R735.7[医药卫生—肿瘤]