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
作者：万杨(四川大学生命科学学院生长代谢与衰老研究中心)；吕涛(四川大学生命科学学院生长代谢与衰老研究中心)；肖智雄(四川大学生命科学学院生长代谢与衰老研究中心)
Author：WAN Yang(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)；LV Tao(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)；XIAO Zhi-Xiong(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)
收稿日期：2015-03-01 年卷（期）页码：2016,53(3):657-663
期刊名称：四川大学学报: 自然科学版
Journal Name：Journal of Sichuan University (Natural Science Edition)
关键字：肿瘤细胞; p53-R273H; E-cadherin; 细胞迁移
Key words：Cancer cell, p53-R273H, E-cadherin, Migration
基金项目：
中文摘要
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。
英文摘要
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.
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