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

Abstract

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 GABPα/β, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPα and β1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPα/β is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.

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Acknowledgements

This work was supported by a grant from the Canadian Breast Cancer Research Initiative. Additional support came from Cancer Care Ontario and the Queen's University Faculty of Medicine. We would like to thank Steve McKnight for the gift of the mouse GABP cDNAs and Drs J-I Sawada and H Hanada for the human GABP monoclonal antibodies.

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Atlas, E., Stramwasser, M., Whiskin, K. et al. GA-binding protein α/β is a critical regulator of the BRCA1 promoter. Oncogene 19, 1933–1940 (2000). https://doi.org/10.1038/sj.onc.1203516

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