GA-binding protein α/β is a critical regulator of the BRCA1 promoter

被引:42
作者
Atlas, E [1 ]
Stramwasser, M [1 ]
Whiskin, K [1 ]
Mueller, CR [1 ]
机构
[1] Queens Univ, Dept Biochem, Can Res Labs, Kingston, ON K7L 3N6, Canada
关键词
BRCA1; expression; GABP alpha/beta; breast cancer;
D O I
10.1038/sj.onc.1203516
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced effect in T47D cells, The main transcription factor interacting with this site was identified as GABP alpha/beta, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells, Cotransfection experiments with GABP alpha and beta 1 expression vectors produced transactivation of this element in both lines, These results suggest that GABP alpha/beta is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.
引用
收藏
页码:1933 / 1940
页数:8
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