Regulation of the BRCA1 promoter in ovarian surface epithelial cells and ovarian carcinoma cells

Graves, Marcia L.; Zhou, Lixin; MacDonald, Gwen; Mueller, Christopher R.; Roskelley, Calvin D.

doi:10.1016/j.febslet.2007.03.072

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Volume 581, Issue 9 , Pages 1825-1833, 1 May 2007

Regulation of the BRCA1 promoter in ovarian surface epithelial cells and ovarian carcinoma cells

Edited by Varda Rotter

This manuscript is dedicated to the memory of Laura Sweet

Marcia L. Graves
- Life Sciences Institute, Department of Cellular and Physiological Sciences, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
Lixin Zhou
- Life Sciences Institute, Department of Cellular and Physiological Sciences, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
Gwen MacDonald
- Cancer Research Laboratories, Department of Biochemistry and Pathology, Queen’s University, Kingston, ON, Canada K7L 3N6
Christopher R. Mueller
- Cancer Research Laboratories, Department of Biochemistry and Pathology, Queen’s University, Kingston, ON, Canada K7L 3N6
- These two senior authors contributed equally to this work.
Calvin D. Roskelley
- Life Sciences Institute, Department of Cellular and Physiological Sciences, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
- Corresponding author. Fax: +1 604 822 2316.
- These two senior authors contributed equally to this work.

Received 28 November 2006; received in revised form 20 March 2007; accepted 27 March 2007. published online 04 April 2007.

Abstract

As BRCA1 expression is often suppressed in sporadic ovarian carcinoma we characterized the regulation of the 231nt proximal ‘L6’ fragment of the BRCA1 promoter in two human ovarian surface epithelial cell and two sporadic ovarian carcinoma cell lines. Two individual regulatory elements within L6, the ‘RIBS’ element and the potential ‘CRE’ element were each necessary, but alone not sufficient for L6 activation in all four cell lines. The latter element showed some affinity for the CREB transcription factor, but cAMP pathway stimulation failed to promote its activation. This element did, however, interact with, and was activated by, c-Jun and Fra2 which suggests that it can interact with AP1-like transcription factors and that it may act co-operatively with RIBS-binding factors to regulate BRCA1 transcription in ovarian cells.

Keywords: BRCA1, Promoter, Transcription, Ovarian cancer, Tumor suppressor