Yokozaki H, Yasui W, Tahara E
First Department of Pathology, Hiroshima University School of Medicine, Japan.
Int Rev Cytol. 2001;204:49-95. doi: 10.1016/s0074-7696(01)04003-7.
Genetic and epigenetic alterations of multiple cancer-related genes and molecules are implicated in the development and progression of human gastric carcinomas. Reactivation of telomerase, inactivation of p53 tumor suppressor gene, overexpression of cyclin E, and reduced expression of p27 KIP1 by disorganized degradation in proteasome are common events of both well-differentiated and poorly differentiated gastric adenocarcinomas. Inactivation of hMLH1 mismatch repair gene by CpG hypermethylation resulting in microsatellite instability, amplification of c-erbB2 oncogene, inactivation of APC tumor suppressor gene, and K-ras mutations are preferentially associated with well-differentiated gastric cancer. Conversely, reduction or loss of E-cadherin and catenins by both mutation and CpG hypermethylation and K-sam and c-met oncogene amplification are necessary for the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cancer cells expressing c-met and hepatocyte growth factor from stromal cells is implicated in morphogenesis of gastric cancer.
多种癌症相关基因和分子的遗传及表观遗传改变与人类胃癌的发生和发展有关。端粒酶的重新激活、p53肿瘤抑制基因的失活、细胞周期蛋白E的过表达以及蛋白酶体中无序降解导致的p27 KIP1表达降低，是高分化和低分化胃腺癌的常见事件。CpG高甲基化导致hMLH1错配修复基因失活从而引起微卫星不稳定、c-erbB2癌基因扩增、APC肿瘤抑制基因失活以及K-ras突变，这些情况优先与高分化胃癌相关。相反，E-钙黏蛋白和连环蛋白因突变和CpG高甲基化而减少或缺失以及K-sam和c-met癌基因扩增，对于低分化或硬癌性胃癌的发生和发展是必要的。表达c-met的癌细胞与基质细胞产生的肝细胞生长因子之间的相互作用与胃癌的形态发生有关。
