alexa Effects of BRCA1 Knockdown on CYP19a1/Aromatase and Ste
ISSN: 1747-0862

Journal of Molecular and Genetic Medicine
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Research Article

Effects of BRCA1 Knockdown on CYP19a1/Aromatase and Steroid Receptor Expression in Ovarian and Tubal Cells

Jean S Fleming1*, Igor Ruza1, Bryony A Thompson2, Kai-Fai Lee3, and Adele G Woolley4

 

1Department of Anatomy, The University of Otago School of Medical Sciences; New Zealand

2Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, QLD, Australia

3Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, China

4The Cell Transformation Group, Department of Pathology, Dunedin School of Medicine, PO Box 913, Dunedin, New Zealand

Corresponding Author:
Emerita Jean S Fleming
Department of Anatomy
Otago School of Medical Sciences
University of Otago
O Box 56, Dunedin, New Zealand 9054
Tel: +644 9023489
E-mail: [email protected]

Received date: July 27, 2015; Accepted date: October 01, 2015; Published date: October 08, 2015

Citation: Fleming JS, Ruza I, Thompson BA, Lee KF, Woolley AG (2015) Effects of BRCA1 Knockdown on CYP19a1/Aromatase and Steroid Receptor Expression in Ovarian and Tubal Cells. J Mol Genet Med 9:185. doi:10.4172/1747-0862.1000185

Copyright:© 2015 Fleming JS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

BRCA1 mutation carriers have an increased lifetime risk of serous epithelial ovarian cancer (EOC), as well as breast cancer, but reasons for this increased risk remain elusive. We hypothesized that the reported relationship between cytochrome P450 aromatase (CYP19a1) and BRCA1 expression might be used to elucidate this pathway to EOC in women with BRCA1 mutations. Expression of BRCA1, CYP19a1 and steroid receptors was measured by qRT-PCR and immunoblotting in immortalized cell lines from the ovarian surface epithelium (hOSE17-1 and hOSE11-12), tubal epithelium (OE-E6/E7) and granulosa cell tumor (KGN), as well as MCF-7 mammary carcinoma cells, before and after BRCA1 knockdown with 2 nM siRNA, or stimulation of CYP19a1 expression with forskolin or phorbol-12-myristate-13-acetate (PMA). Low or no CYP19a1 expression was observed in all cell lines, except KGN cells. BRCA1 knockdown with 2 nM siRNA did not stimulate CYP19a1 expression in any cell line. Forskolin treatment increased CYP19a1 expression only in KGN cells and this resulted in a decrease in BRCA1 expression equivalent to 2 nM siRNA knockdown. We conclude that lowering BRCA1 expression in OSE and tubal epithelia cell lines does not stimulate CYP19a1 expression or change steroid receptor expression significantly. The mechanism by which BRCA1 mutation increases risk of serous EOC remains to be elucidated.

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