前列腺癌与雌激素受体基因启动子甲基化关系的实验研究

Experimental study on relationship between CpG methylation of estrogen receptor gene promoter and progression of prostate cancer

目的 探讨前列腺癌雌激素受体 (ER)的失活与其基因启动子甲基化的关系。方法 采用亚硫酸氢盐基因组测序法研究前列腺癌细胞系和显微解剖的前列腺癌标本的ER基因的甲基化状态。结果 前列腺癌细胞系ER基因启动子的甲基化率为 6 /6 ,且ERmRNA均不表达。将这些细胞用去甲基剂 5 氮 2 脱氧胞苷处理可以恢复所有ER阴性细胞系的ERmRNA的表达。 80 % (8/10 )的低分级前列腺癌 (Ⅰ、Ⅱ级 )和 95 % (2 0 /2 1)的高分级前列腺癌 (Ⅲ～Ⅴ级 )表现出ER基因启动子甲基化。结论 前列腺癌细胞ER基因启动子的异常甲基化可以导致该基因失活。在恶性度高的细胞 ,这种现象更为普遍。

Objective\ To investigate the inactivation of estrogen receptor (ER) in prostate cancer and its relation with methylation of gene promoter. Methods\ By using bisulfite genomic sequencing method, the methylation status of ER gene was studied in the prostate cancer cell line and microdissected prostate cancer samples. Results\ The ER gene promoter in prostate cancer cell line was methylated in 100%. ER mRNA was not expressed. Treatment of those cell lines with demethylating agent 5-aza-2-deoxycytidine restored ER mRNA expression in all the ER-negative cell lines. Of the prostate cancer tissue samples analyzed, 80% (8/10) in the low-grade group (grade Ⅰ and Ⅱ) and 95% (20/21) in the high-grade group (grade Ⅲ～Ⅴ) exhibited promoter methylation of ER gene. Conclusions\ The abnormal methylation of ER gene promoter in prostate cancer could result in the inactivation of ER gene. In the high malignant cells, this phenomenon was more common.\;