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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >SILENCING OF THE E-CADHERIN INVASION-SUPPRESSOR GENE BY CPG METHYLATION IN HUMAN CARCINOMAS
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SILENCING OF THE E-CADHERIN INVASION-SUPPRESSOR GENE BY CPG METHYLATION IN HUMAN CARCINOMAS

机译：CPG甲基化对人癌中E-钙粘蛋白侵袭抑制基因的沉默

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摘要

E-Cadherin, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations, In an attempt to clarify the mechanism responsible for inactivation of this gene in carcinomas, we investigated the methylation state around the promoter region by digestion of DNA with the methylation-sensitive restriction enzyme Hpa II, as CpG methylation of the promoter has been postulated to be a mechanism of transcriptional inactivation of some genes, We found that E-cadherin expression-negative carcinoma cell lines were accompanied by the hypermethylation state, whereas E-cadherin-positive cell lines were not, Furthermore, treatment of E-cadherin-negative carcinoma cells with the demethylating agent 5-azacytidine resulted in reexpression of the gene and reversion of scattered spindle-shaped cells to cells with epithelial morphology, These results suggest that hypermethylation around the promoter may be a mechanism of E-cadherin inactivation in human carcinomas and that treatment of E-cadherin-inactivated cells with a demethylating agent may cause gene expression reversion leading to epithelial morphogenesis with acquisition of the hemophilic cell-cell adhesive property. [References: 36]
机译：E-钙黏着蛋白是一种细胞黏附分子，在维持上皮表型中起着关键作用，从体外实验和临床观察中积累的证据来看，E-钙黏着蛋白被认为是一种侵袭抑制基因，试图阐明造成这种现象的机制。该基因在癌症中的失活，我们通过用甲基化敏感的限制性酶Hpa II消化DNA来研究了启动子周围的甲基化状态，因为该启动子的CpG甲基化被认为是某些基因转录失活的机制，我们发现E-cadherin表达阴性的癌细胞系伴有高甲基化状态，而E-cadherin阳性细胞系则不伴有高甲基化状态。此外，用去甲基化剂5-氮胞苷处理E-cadherin阴性癌细胞导致基因的重新表达，使分散的纺锤形细胞恢复为具有上皮形态的细胞，这些结果表明结果表明启动子周围的高甲基化可能是人类癌中E-钙粘蛋白失活的机制，并且用去甲基化剂处理E-钙粘蛋白失活的细胞可能导致基因表达逆转，从而导致上皮细胞形态发生并获得了嗜血细胞-细胞黏附剂属性。 [参考：36]

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