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小窝蛋白-1调控人乳腺癌细胞中BRCA1基因的表达及细胞定位。

Caveolin-1 controls BRCA1 gene expression and cellular localization in human breast cancer cells.

作者信息

Glait Chen, Ravid Dana, Lee Sam W, Liscovitch Mordechai, Werner Haim

机构信息

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

出版信息

FEBS Lett. 2006 Oct 2;580(22):5268-74. doi: 10.1016/j.febslet.2006.08.071. Epub 2006 Sep 11.

Abstract

The role of caveolae and the caveolin proteins in cancer has been the subject of extensive research. BRCA1 participates in multiple biological pathways including DNA damage repair, transcriptional control, cell growth, apoptosis, and others. Little information, however, is available regarding the cellular mechanisms that control BRCA1 gene expression. The present study examined the potential regulation of BRCA1 gene expression and subcellular localization by Cav-1. Results of Western blots, RT-PCR, and transfection experiments showed that Cav-1 enhances BRCA1 protein and mRNA levels via a mechanism that involves transactivation of the BRCA1 promoter and which is p53-dependent. In addition, immunostaining experiments demonstrate that Cav-1 induced the cytoplasmic sequestration of BRCA1.

摘要

小窝和小窝蛋白在癌症中的作用一直是广泛研究的主题。BRCA1参与多种生物学途径,包括DNA损伤修复、转录调控、细胞生长、细胞凋亡等。然而,关于控制BRCA1基因表达的细胞机制的信息却很少。本研究检测了Cav-1对BRCA1基因表达和亚细胞定位的潜在调控作用。蛋白质免疫印迹、逆转录-聚合酶链反应及转染实验结果表明,Cav-1通过一种涉及BRCA1启动子反式激活且依赖p53的机制提高BRCA1蛋白和mRNA水平。此外,免疫染色实验表明,Cav-1诱导BRCA1在细胞质中隔离。

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