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Modulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppression

Oncogene volume 24, pages 8343–8348 (2005)Cite this article

Abstract

Mutations in BRCA1 increase risks of familial breast and ovarian cancers, particularly among premenopausal women. While BRCA1 plays an active role in DNA repair, this function alone may not be sufficient to explain why BRCA1-associated tumors predominantly occur in estrogen-responsive tissues. Aromatase is the rate-limiting enzyme in estrogen biosynthesis and a key target in breast cancer treatment. Aromatase expression in ovarian granulosa cells dictates levels of circulating estrogen in premenopausal women, and its aberrant overexpression in breast adipose tissues promotes breast cancer growth. Here, we show that BRCA1 modulates aromatase expression in ovarian granulosa cells and primary preadipocytes. The cyclic AMP-dependent expression of aromatase in ovarian granulosa cells is inversely correlated with the protein level of BRCA1. Importantly, transient knockdown of BRCA1 enhances aromatase expression in both ovarian granulosa cells and primary preadipocytes. We propose that BRCA1 deficiency in epithelial and certain nonepithelial cells may result in combined effects of aberrant estrogen biosynthesis and compromised DNA repair capability, which in turn may lead to specific cancers in the breast and ovary.

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Acknowledgements

We thank Dr Toshihiko Yanase for the KGN cell line. We also thank Drs Richard Santen, Margaret Shupnik, and Anindya Dutta. This study was supported by a grant to RL from the National Cancer Institute (CA093506), and to YH from the Department of Defense Breast Cancer Research Program (DAMD17-03-1-0398).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, 22908, VA, USA

    Yanfen Hu, Sagar Ghosh, Asma Amleh & Rong Li

  2. Department of Medicine and Division of Endocrinology, School of Medicine, University of Virginia, Charlottesville, 22908, VA, USA

    Wei Yue

  3. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, China

    Yunzhe Lu

  4. Department of Plastic and Reconstructive Surgery, School of Medicine, University of Virginia, Charlottesville, 22908, VA, USA

    Adam Katz

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  1. Yanfen Hu
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Correspondence to Yanfen Hu or Rong Li.

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Hu, Y., Ghosh, S., Amleh, A. et al. Modulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppression. Oncogene 24, 8343–8348 (2005). https://doi.org/10.1038/sj.onc.1208985

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