Kunze Ekkehard, Schlott Thilo
Department of Osteopathology and Haematopathology, University of Göttingen, Göttingen, Germany.
Int J Mol Med. 2007 Oct;20(4):557-63.
The molecular mechanisms underlying the histogenesis of nonurothelial carcinomas of the urinary bladder are not yet clearly understood. There is a growing body of evidence that, generally, epigenetic regulation mediated by methylation of normally unmethylated CpG islands at the 5' promoter regions of genes is involved in the modification of tumorigenesis. This prompted the current study to explore the methylation status of a broad panel of various genes implicated in cell differentiation and tumor suppression in 10 adenocarcinomas and 6 signet ring cell carcinomas of the bladder. Using methylation-specific PCR, we were able to detect a high frequency of promoter methylation of the 14-3-3 sigma (100%) and CAGE-1 (80%) genes in adenocarcinomas, and in nearly all signet ring cell carcinomas. The SYK and hDAB2IP genes proved to be hypermethylated in only single cases, whereas the caveolin-1 gene failed to be hypermethylated in all cases. The present data suggest that promoter methylation of the 14-3-3 sigma and CAGE-1 genes plays a crucial role during the phenotypical morphogenesis of vesical adenocarcinomas including signet ring cell carcinomas by an epigenetic mechanism.
膀胱非尿路上皮癌组织发生的分子机制尚未完全明确。越来越多的证据表明，一般来说，由基因5'启动子区域正常未甲基化的CpG岛甲基化介导的表观遗传调控参与肿瘤发生的修饰。这促使本研究探讨10例膀胱腺癌和6例膀胱印戒细胞癌中一系列与细胞分化和肿瘤抑制相关的各种基因的甲基化状态。使用甲基化特异性PCR，我们能够在腺癌以及几乎所有印戒细胞癌中检测到14-3-3 sigma（100%）和CAGE-1（80%）基因启动子甲基化的高频率。SYK和hDAB2IP基因仅在个别病例中被证明高度甲基化，而小窝蛋白-1基因在所有病例中均未发生高度甲基化。目前的数据表明，14-3-3 sigma和CAGE-1基因的启动子甲基化通过表观遗传机制在包括印戒细胞癌在内的膀胱腺癌表型形态发生过程中起关键作用。
