子宫内膜癌及正常子宫内膜组织中PR基因启动子区CpG岛甲基化对比探究.docVIP

子宫内膜癌及正常子宫内膜组织中PR基因启动子区CpG岛甲基化对比探究【摘要】 目的 研究子宫内膜癌中孕激素受体亚型PRA、PRB表达与其启动子区甲基化状态的关系, 探讨子宫内膜癌组织、细胞分子变化特征及孕激素受体亚型表达下调的机制。方法 ①应用免疫组化SP法检测子宫内膜癌组织中PRA、PRB蛋白的表达。②应用甲基化特异性PCR 检测子宫内膜癌组织及经5,杂氮脱氧胞苷(ADC)处理前后子宫内膜癌Hec,1,B细胞系中PRA、PRB的甲基化状态。③应用免疫印迹法检测ADC处理Hec,1,B细胞系前后PRA、PRB蛋白的表达。结果 ①与正常子宫内膜组织比较:PRA蛋白在高、中低分化子宫内膜癌组织中表达差异无统计学意义；PRB蛋白在高分化子宫内膜癌组织中表达无明显降低，差异无统计学意义，在中低分化子宫内膜癌组织中表达明显降低，差异有统计学意义。②与正常子宫内膜组织比较，子宫内膜癌组织中，PRA启动子区CpG岛甲基化率较低，差异无统计学意义，PRB启动子区CpG岛甲基化率较高，差异有统计学意义，与组织分化程度有关，与病理类型及有无淋巴结转移和有无肌层浸润无关。结论 子宫内膜癌组织以及Hec,1,B细胞系中，存在PR基因异常甲基化，ADC可通过去甲基化作用使PRB 恢复表达，可能提高子宫内膜癌的临床内分泌治疗效果 【关键词】 子宫内膜癌；孕激素受体亚型；甲基化 Research express defect and CpG promotor region methylation of progesterone receptor gene in human uterine endometrial carcinoma TIAN Hai,xia.Department of Gynaecology and obstetrics,Centre Peoples Hospital of Siping,Siping 136000,China 【Abstract】 Objective Study the relationship between PRA and PRB expression and promoter methylation status in the endometrial cancer, to explore the molecular characteristics and expression of progesterone receptor isoforms downward mechanism.Methods Application of immunohistochemical and methylation,specific PCR to detect PRA and PRB protein expression in the endometrial carcinoma tissues. Results ① Compared with normal endometrial tissues, PRA protein were not significantly reduce,PRB protein in well,differentiated endometrial carcinoma were not significantly lower, in poorly differentiated endometrial cancer tissues decreased. ② PRA promoter region CpG island methylation rate is not significant difference, PRB was relatively high, related with the degree of differentiation, unrelated with pathological type and lymph node metastasis and muscularis infiltrates. Conclusion Endometrial cancer tissues and cell lines, existence of abnormal methylation of PR gene, maybe involved in the formation of endometrial cancer. 【Key words】 Endometrial carcinoma; Progesterone receptor isoform;Methylation 子宫内膜癌(endometrial carcinoma)为女性生殖器三大恶性肿瘤之一，近年发病率有上升趋势［1］。子