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目的探讨前列腺癌组织中DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)的表达与谷胱甘肽S转移酶P1(glutathione S transferase P1,GSTP1)、结肠腺瘤性息肉病(adenomatous polyposis coli,APC)甲基化状态的关系及临床意义。方法采用RT-PCR的方法检测56例前列腺癌(prostate cancer,PCa)组织和10例前列腺增生(benign prostatichyperplasia,BPH)组织中DNMT1和GSTP1、APC的mRNA表达,采用甲基化特异性PCR(MS-PCR)的方法检测GSTP1、APC的启动子区CpG岛甲基化状态。结果大多数PCa组织中DNMT1 mRNA高表达(在低分化癌中阳性率为90.0%),而GSTP1和APC低表达(在低分化癌中阳性率分别为23.3%和33.3%),BPH组织中DNMT1 mRNA低表达(40.0%),而GSTP1和APC高表达(分别为90.0%和80.0%),低分化癌与BPH相比,差异有统计学意义(P<0.05);大多数PCa组织中GSTP1、APC启动子区CpG岛呈高甲基化状态(在低分化癌中阳性率分别为83.3%和73.3%),而BPH组织中呈低甲基化(阳性率分别为10.0%和20.0%),低分化癌与BPH相比,差异有统计学意义(P<0.05)。结论 PCa组织中GSTP1、APC失活的机制可能与DNMT1的高表达导致其启动子区CpG岛异常高甲基化有关。
Objective To investigate the relationship between the expression of DNA methyltransferase 1 (DNMT1) and the expression of glutathione S transferase P1 (GSTP1), adenomatous polyposis coli APC) methylation status and its clinical significance. Methods The mRNA expressions of DNMT1, GSTP1 and APC in 56 cases of prostate cancer (PCa) and 10 cases of benign prostatichyperplasia (BPH) were detected by RT-PCR. The methylation-specific PCR (MS) -PCR) was used to detect the methylation status of CpG island in the promoter regions of GSTP1 and APC. Results DNMT1 mRNA was overexpressed in most PCa tissues (positive rate was 90.0% in poorly differentiated carcinoma), while GSTP1 and APC were low (23.3% and 33.3% respectively in poorly differentiated carcinoma). DNMT1 (40.0%), while GSTP1 and APC were overexpressed (90.0% and 80.0%, respectively). There was a significant difference between poorly differentiated carcinoma and BPH (P <0.05). Most of the PCa tissues had GSTP1, The CpG island of APC promoter was highly methylated (83.3% and 73.3%, respectively) in poorly differentiated cancers, whereas it was hypomethylated in BPH tissues (positive rates were 10.0% and 20.0%, respectively) Compared with BPH, the difference was statistically significant (P <0.05). Conclusion The mechanism of inactivation of GSTP1 and APC in PCa may be related to the abnormal hypermethylation of CpG island in promoter region due to the high expression of DNMT1.