卵巢上皮性癌中RIZ1基因表达缺陷的意义及其与甲基化的关系  

Changes of RIZ1 Gene Expression in Epithelial Ovarian Cancer and the Mechanism

作　　者：蔡惠兰[1] 钱颖[1] 贺晓琪[1] 王泽华[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,湖北武汉430022

出　　处：《武汉大学学报（医学版）》2008年第4期430-434,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:30070786)

摘　　要：目的:研究抑癌基因RIZ1在卵巢上皮性癌组织及卵巢癌细胞系中的表达变化,分析其表达变化与甲基化的关系。方法:以卵巢癌组织及卵巢癌细胞系为研究对象。RT-PCR检测RIZ1 mRNA水平;MSP检测RIZ1基因甲基化状况;蛋白印迹检测RIZ1蛋白表达。结果:卵巢癌组织、卵巢癌细胞系及正常卵巢组织中RIZ1 mRNA相对含量的平均值分别为0.32±0.14,0.26±0.11和1.17±0.08。RIZ1蛋白相对含量的平均值分别为0.38±0.11,0.34±0.06和1.56±0.14。卵巢癌组织及卵巢癌细胞系中RIZ1的甲基化率分别为25.8%、20%。卵巢癌组织、卵巢癌细胞系分别与正常卵巢组织比较,RIZ1基因的表达差异均有统计学意义(P<0.05);存在甲基化的卵巢癌组织及细胞系中,RIZ1基因表达缺失或下降。5-杂氮-2′-脱氧胞苷处理RIZ1基因发生甲基化的卵巢癌细胞系后,RIZ1基因重表达;且去甲基化处理后,卵巢癌细胞生长均减慢。结论:RIZ1基因表达缺陷与卵巢癌的发生有关,DNA甲基化是其表达缺陷的原因之一;去甲基化处理可使RIZ1基因重表达,并抑制卵巢癌细胞的增殖。Objective： To evaluate the expression of RIZ1 gene in epithelial ovarian cancer and to analyze the relationship between this alteration and the promoter hyper-methylation of RIZ1 gene. Methods： The RIZ1 mRNA expression was detected by RT-PCR and the RIZ1 proptein was examined by Western blot. Methylation-specific PCR （MSP） was used to assay the methylation of RIZ1 promotor region. Results： The expression of RIZ1 mRNA and protein were lost or decreased significantly in all ovarian cancer tissues and cell lines. The methylation rate was 25.8% （8/31） and 40% （2/5） in ovarian cancer tissue specimens and ovarian cancer cell lines respective- ly. Compared that in with normal ovary specimens, the RIZ1 gene expression level decreased significantly in ovarian cancer specimens and cell lines （both P〈0.05） and was partly due to the methylation of RIZ1 gene. 5-Aza-CdR could reactivate the expression of RIZ1 gene in methylated cells and inhibit the cells growth in vivo. Conclusion： Down-regulation of RIZ1 gene expression plays an important role in the development of ovarian cancer, and this alteration is partially caused by RIZ1 methylation.

关 键 词：卵巢肿瘤 RIZ1基因 RIZ1蛋白 DNA甲基化 

分 类 号：R737.31[医药卫生—肿瘤]