p53突变蛋白下调调控人肺腺癌细胞中E-cadherin的表达并促进细胞迁移

Mutant p53 Down-regulates E-Cadherin Expression in Human Lung Adenocarcinoma Cells to Enhance Cell Migration

摘要:

摘要：p53 是最重要的抑癌基因之一。在肿瘤发生发展过程中，超过50% 的人类肿瘤组织和细胞中存在 p53 基因发生突变，而且大多数为点突变，其中包括 R273H，由此产生的点突变蛋白会失去 p53 的DNA结合和特异的转录活性。最近的研究表明p53突变蛋白还可能获得一些野生型p53蛋白不具有的新的生物学活性。在本研究中，我们在人肺肿瘤细胞 H1299 中稳定表达含R273H 点突变的p53 蛋白（p53-R273H），观察到细胞中 E-cadherin mRNA 和蛋白水平下调，同时细胞迁移能力增强。免疫荧光方法检测发现 p53-R273H 显著降低 E-cadherin 在肿瘤细胞间的表达。这些结果表明p53-R273H 突变蛋白具有下调 E-cadherin 基因的表达和促使肿瘤细胞迁移的新功能。

Abstract:

Abstract: p53 is one of the most important tumor suppressor genes, which is mutated in more than 50% human cancers. The most common mutations in the p53 gene are single nucleotide point mutations, which leads to an amino acid replacement resulting in loss of DNA-binding and transactivating activities. In this study, stably-expressing p53-R273H in H1299 human lung cancer cells promoted cell migration and concomitant of down-regulated E-cadherin expression. Immunofluorescent staining showed reduced E-cadherin at cell-cell junction. Together, these data suggest that mutant p53-R273H protein acquires a new activity in down-regulating E-cadherin expression and promoting cancer cell migration.