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

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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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References

  • Antoniou A, Pharoah PDP, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg Å, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjäkoski K, Kallioniemi O-P, Thompson D, Evans C, Peto J, Lalloo F, Evans DG and Easton DF . (2003). Am. J. Hum. Genet., 72, 1117–1130.

  • Baer R and Ludwig T . (2002). Curr. Opin. Genet Dev., 12, 86–91.

  • Bulun SE, Sebastian S, Takayama K, Suzuki T, Sasano H and Shozu M . (2003). J. Steroid Bioc. Mol. Biol., 86, 219–224.

  • Chen S, Zhou D, Yang C, Okubo T, Kinoshita Y, Yu B, Kao Y-C and Itoh T . (2001). J. Steroid Bioc. Mol. Biol., 79, 35–40.

  • Chodankar R, Kwang S, Sangiorgi F, Hong H, Yen H-Y, Deng C, Pike MC, Shuler CF, Maxson R and Dubeau L . (2005). Curr. Biol., 15, 561–565.

  • Ghosh S, Wu Y, Hu Y-F and Li R . (2005). Oncogene, 24, 2236–2246.

  • Hu Y-H and Li R . (2002). Genes Dev., 16, 1509–1517.

  • Huo Z, Giger ML, Olopade OI, Wolverton DE, Weber BL, Metz CE, Zhong W and Cummings SA . (2002). Radiology, 225, 519–526.

  • Joukov V, Chen J, Fox EA, Green JB and Livingston D . (2001). Proc. Natl. Acad. Sci. USA, 98, 12078–12083.

  • Katz AJ, Tholpady A, Tholpady SS, Shang H and Ogle RC . (2005). Stem Cells, 23, 412–423.

  • Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L and Offit K . (2002). N. Engl. J. Med., 346, 1609–1615.

  • Key TJ and Verkasalo PK . (1999). Breast Cancer Res., 1, 18–21.

  • Marquis ST, Rajan JV, Wynshaw-Boris A, Xu J, Y G-Y, Abel KJ, Weber BL and Chodosh LA . (1995). Nat. Genet., 11, 17–26.

  • McCarthy EE, Celebi JT, Baer R and Ludwig T . (2003). Mol. Cell. Biol., 23, 5056–5063.

  • Nishi Y, Yanase T, Mu YM, Oba K, Ichino I, Saito M, Nomura M, Mukasa C, Okabe T, Goto K, Takayanagi R, Kashimura Y, Haji M and Nawata H . (2001). Endocrinology, 142, 437–445.

  • Phillips KW, Goldsworthy SM, Bennett LM, Brownlee HA, Wiseman RW and Davis BJ . (1997). Lab. Inves., 76, 419–425.

  • Rajan JV, Marquis ST, Gardner HP and Chodosh LA . (1997). Dev. Biol., 184, 385–401.

  • Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van'T Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E, Olopade OI and Weber BL . (2002). New Engl. J. Med., 346, 1616–1622.

  • Richards JS . (1994). Endo. Rev., 15, 725–751.

  • Richards JS . (2001). Mol. Endocrinol., 15, 209–218.

  • Sasano H and Harada N . (1998). Endocrine Rev., 19, 583–607.

  • Simpson ER, Clyne C, Rubin G, Boo WC, Robertson K, Britt K, Speed C and Jones M . (2002). Annu. Rev. Physiol., 64, 93–127.

  • Simpson ER and Davis SR . (2001). Endocrinology, 142, 4589–4594.

  • Starita LM and Parvin JD . (2003). Curr. Opin. Cell Biol., 15, 345–350.

  • Tekmal RR, Kirma N, Gill K and Fowler K . (1999). Endocrine-Related Cancer, 6, 307–314.

  • Turner KJ, Macpherson S, Millar MR, McNeilly AS, Williams K, Cranfield M, Groome NP, Sharpe RM, Fraser HM and Saunders PTK . (2002). J. Endocrinol., 172, 21–30.

  • Venkitaraman AR . (2002). Cell, 108, 171–182.

  • Yue W and Brodie AMH . (1997). J. Steroid Biochem. Mol. Biol., 63, 317–328.

  • Zhou D and Chen S . (1999). Arch. Biochem. Biophys., 371, 179–190.

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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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  2. Sagar Ghosh
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  3. Asma Amleh
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  4. Wei Yue
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  5. Yunzhe Lu
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  7. Rong Li
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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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  • DOI: https://doi.org/10.1038/sj.onc.1208985

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