GA-binding protein α/β is a critical regulator of the BRCA1 promoter
GA-binding protein α/β is a critical regulator of the BRCA1 promoter
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DOI：
10.1038/sj.onc.1203516
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发表时间：
2000-04-06
期刊：
影响因子：
8
通讯作者：
Mueller, CR
中科院分区：
文献类型：
--
作者：
Atlas, E;Stramwasser, M;Mueller, CR
BRCA1表达降低可能在散发性乳腺癌的发病机制中起一定作用。对BRCA1 1a启动子近端的缺失和点突变分析表明，该启动子在MCF-7细胞中是表达启动子的关键区域，但在T47D细胞中的作用明显减弱，与该区域相互作用的主要转录因子是GABPα/β，并且只在MCF-7细胞的核提取液中观察到离散的DNA结合复合体，与GABPα和β1表达载体共转染实验在两种细胞中都产生了该元件的反式激活，这些结果表明GABPα/β是BRCA1表达的关键激活子，其活性可能在人乳腺癌细胞系中有所不同。
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.