Wang Yang, Yu Jing, Zhan Qimin
State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Pan Jia Yuan Nan Li, Beijing 100021, China.
Biochem Biophys Res Commun. 2008 May 30;370(2):201-6. doi: 10.1016/j.bbrc.2008.03.031. Epub 2008 Mar 14.
BRCA1 is involved in multiple biological processes including DNA damage repair, cell growth, apoptosis, and transcriptional activation. Also, BRCA1 plays key roles in inhibiting cancer progression. Caveolin-1 is identified as a tumor suppressor and regulates the invasiveness of cells. However, the interactions between BRCA1 and caveolin-1 remain largely unknown. We have investigated the potential function of BRCA1 in regulation of caveolin-1 gene expression and its subcellular localization as well. The observations from RT-PCR, transfection, RNAi, and luciferase assays implied that BRCA1 could elevate caveolin-1 mRNA levels via transactivation of the caveolin-1 promoter region. Additionally, immunofluorescent approach showed that BRCA1 might inhibit the invasiveness and metastatic abilities of mammalian cells by inducing the redistribution of caveolin-1 from the cytoplasm to the cell membrane.
BRCA1参与多种生物学过程,包括DNA损伤修复、细胞生长、细胞凋亡和转录激活。此外,BRCA1在抑制癌症进展中起关键作用。小窝蛋白-1被鉴定为一种肿瘤抑制因子,并调节细胞的侵袭性。然而,BRCA1与小窝蛋白-1之间的相互作用在很大程度上仍不清楚。我们研究了BRCA1在调节小窝蛋白-1基因表达及其亚细胞定位方面的潜在功能。来自逆转录聚合酶链反应(RT-PCR)、转染、RNA干扰(RNAi)和荧光素酶测定的观察结果表明,BRCA1可通过反式激活小窝蛋白-1启动子区域来提高其信使核糖核酸(mRNA)水平。此外,免疫荧光方法显示,BRCA1可能通过诱导小窝蛋白-1从细胞质重新分布到细胞膜来抑制哺乳动物细胞的侵袭和转移能力。