Li L C, Zhao H, Nakajima K, Oh B R, Ribeiro Filho L A, Carroll P, Dahiya R
Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California, USA.
J Urol. 2001 Aug;166(2):705-9.
We studied the methylation status of E-cadherin gene promoter in prostate cancer and its relationship with E-cadherin inactivation in prostate cancer.
Seven human prostate cell lines and 35 microdissected prostate cancer specimens were analyzed for E-cadherin promoter methylation using the bisulfite genome sequencing technique. E-cadherin messenger (m)RNA expression and protein expression were also studied in prostate cell lines by reverse transcriptase-polymerase chain reaction and in prostate cancer specimens by immunostaining, respectively.
The overall methylation of E-cadherin promoter was evident in 14 of 20 grades III to V (70%) and in 5 of 15 grades I to II (33%) prostate cancer samples. It correlated with absent or reduced E-cadherin immunostaining. Methylation in low grade tumors was present mainly in the exon region, whereas in high grade tumors methylation was also present in the promoter region. Methylation was noted in 2 of 6 prostate cancer cell lines (33%) and correlated well with decreased E-cadherin mRNA in these cell lines. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored E-cadherin mRNA levels in the E-cadherin negative prostate cancer cell lines TSUPr1 and DuPro.
Methylation of the E-cadherin gene is common in prostate cancer and the severity of E-cadherin methylation correlates with tumor progression. This study implies that the invasion and metastasis suppressor function of E-cadherin may often be compromised in human prostate cancer by epigenetic rather than by mutational events.
我们研究了前列腺癌中E-钙黏蛋白基因启动子的甲基化状态及其与前列腺癌中E-钙黏蛋白失活的关系。
使用亚硫酸氢盐基因组测序技术分析了7种人前列腺癌细胞系和35个显微切割的前列腺癌标本中E-钙黏蛋白启动子的甲基化情况。还分别通过逆转录聚合酶链反应研究了前列腺癌细胞系中E-钙黏蛋白信使核糖核酸（mRNA）的表达，并通过免疫染色研究了前列腺癌标本中E-钙黏蛋白的蛋白表达。
在20个III至V级（70%）的前列腺癌样本中，有14个样本的E-钙黏蛋白启动子总体甲基化明显，在15个I至II级（33%）的样本中有5个样本出现这种情况。它与E-钙黏蛋白免疫染色缺失或减少相关。低级别肿瘤中的甲基化主要存在于启动子区域，而高级别肿瘤中的甲基化也存在于启动子区域。在6种前列腺癌细胞系中有2种（33%）出现甲基化，并且与这些细胞系中E-钙黏蛋白mRNA的减少密切相关。用去甲基化剂5-氮杂-2'-脱氧胞苷处理可恢复E-钙黏蛋白阴性前列腺癌细胞系TSUPr1和DuPro中的E-钙黏蛋白mRNA水平。
E-钙黏蛋白基因的甲基化在前列腺癌中很常见，E-钙黏蛋白甲基化的严重程度与肿瘤进展相关。这项研究表明，在人类前列腺癌中，E-钙黏蛋白的侵袭和转移抑制功能可能常常因表观遗传事件而非突变事件而受损。
