Abstract
Transcriptional regulation of the BRCA1 proximal promoter has been suggested to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter reveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 and T-47D cells. This site is shown to be important for the constitutive expression of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP induction. It appears that CREB acts as a constitutive positive element for BRCA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.
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Acknowledgements
We would like to thank Jim Gore for his excellent technical assistance. This work was supported by a grant from the Canadian Breast Cancer Research Initiative and grant BC000072 from the US Department of Defense Breast Cancer Research Program. Additional support came from Cancer Care Ontario and the Queen's University Faculty of Medicine.
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Atlas, E., Stramwasser, M. & Mueller, C. A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element. Oncogene 20, 7110–7114 (2001). https://doi.org/10.1038/sj.onc.1204890
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DOI: https://doi.org/10.1038/sj.onc.1204890
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