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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。
Objective To study the relationship between the expression of progesterone receptor subtypes PRA and PRB and their promoter methylation status in endometrial carcinoma and to explore the mechanism of the down-regulation of the expression of progesterone receptor subtypes and endometrial carcinoma . Methods ① Immunohistochemical SP method was used to detect the expression of PRA and PRB in endometrial carcinoma. ② The methylation status of PRA and PRB in endometrial carcinoma and endometrial carcinoma Hec-1-B cell line before and after treatment with 5-aza-deoxycytidine (ADC) was detected by methylation-specific PCR. ③ Western blotting was used to detect the expression of PRA and PRB before and after treatment of Hec-1-B cell line with ADC. Results ① Compared with normal endometrium, there was no significant difference in the expression of PRA protein between high and moderately differentiated endometrial carcinoma tissues. There was no significant difference in the expression of PRB protein in well differentiated endometrial carcinoma The significance of learning, in poorly differentiated endometrial cancer tissues was significantly lower, the difference was statistically significant. ② Compared with normal endometrial tissue, the methylation rate of CpG island in PRA promoter region was lower in endometrial carcinoma tissues, the difference was not statistically significant, and the methylation rate of CpG island in PRB promoter region was higher Statistical significance, with the degree of tissue differentiation, and pathological type with or without lymph node metastasis and the presence of myometrial invasion has nothing to do. Conclusion Abnormal methylation of PR gene exists in endometrial carcinoma and Hec-1-B cell line. ADC can restore PRB expression through demethylation and may improve clinical endocrine therapy of endometrial carcinoma.