前列腺癌细胞株E-钙粘连素基因启动子甲基化与其表达

目的：了解Ｅ－钙粘连素（Ｅ－ｃａｄ）基因启动子ＣｐＧ位点甲基化与前殂腺癌细胞Ｅ－ｃａｄ基因的失活的关系，并探讨Ｅ－ｃａｄ基因异常甲基化机制。方法：采用硫酸氢钠基因组测序法检测良性前列腺上皮和前列腺癌细胞株的Ｅ－ｃａｄ基因甲基化状态，并采用ＲＴ－ＰＣＲ检测各细胞株Ｅ－ｃａｄ和ＤＮＡ甲基转移酶（Ｄｎｍｔｌ）的ｍＲＮＡ表达。结果：有３３％（２／６）的前列腺癌细胞株发生甲基化现象，相应的细胞株中Ｅ－ｃａｄ

A specific methylation pattern of the E-cadherin gene promoter is associated with its expression in prostate cancer lines

Objective: The present study was designed to test the hypothesis that CpG methylation ofpromoter region may inactivate the E-cadherin (E-cad)gene expression in prostate cancer line, and try tounderstand the mechanism of aberrant methylation. Methods:We studied the methylation status of E-cad gene inhuman prostate normal and cancer cell lines using the bisulfate genome sequencing technique. We also examinedthe expression of the E-cad gene and DNA methyltransferase (Dnmtl)in these lines by RT-PCR. Results:Hypermethylation was found in 33% of prostate cancer cell lines (2/6)and correlated well with decreased E-cadmRNA levels in these cell lines. Treatment with a demethylating agent, 5-aza-2′-deoxycytidine, restored E-cadmRNA levels in E-cad negative prostate cancer cell lines. Cancer cell lines had higher levels of Dnmtl mRNA thannormal cells. Conclusion:Our data clearly demonstrate that hypermethylation of E-cad in prostate cancer is acommon event that leads to the inactivation of the E-cad in prostate cancer is partly resulted by high level Dnmtl.