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| Subject Categories: Chromatin & Transcription | Molecular Biology of Disease |
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| The EMBO Journal
(2004) 23, 2293–2303, doi:10.1038/sj.emboj.7600231 Published online 13 May 2004 |
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| BRG1/BRM and prohibitin are required for growth suppression by estrogen antagonists |
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| Sheng Wang, Baohua Zhang and Douglas V Faller |
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Boston University School of Medicine, Cancer Research Center, Boston, MA, USA To whom correspondence should be addressed Sheng Wang, Boston University School of Medicine, Cancer Research Center, R-906, 715 Albany Street, Boston, MA 02118, USA. Tel.: +1 617 638 5618; Fax: +1 617 638 5609; E-mail: sw184@bu.edu Received 25 November 2003; Accepted 19 April 2004; Published online 13 May 2004. |
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| Abstract |
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| Estrogen antagonists are universally employed in the breast cancer therapy, although antagonist therapy is limited by the inevitable development of cellular resistance. The molecular mechanisms by which these agents inhibit cellular proliferation in breast cancer cells are not fully defined. Recent studies have shown the involvement of the E2F pathway in tamoxifen-induced growth arrest. We show that an E2F repressor, prohibitin, and the chromatin modifiers Brg1/Brm are required for estrogen antagonist-mediated growth suppression through the estrogen receptor, and that their recruitment to native promoter-bound E2F is induced via a JNK1 pathway. In addition, we demonstrate major mechanistic differences among the signaling pathways initiated by estrogen, estrogen deprivation, and estrogen antagonists. Collectively, these findings suggest that the prohibitin/Brg1/Brm node is a major cellular target for estrogen antagonists, and thereby also implicate prohibitin/Brg1/Brm as potentially important targets for breast cancer therapy. |
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| Keywords: E2F, SWI/SNF, tamoxifen, transcription |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHJournal of Cerebral Blood Flow & Metabolism Original Article A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins Nature Immunology Article (01 Jun 2001) Oncogene Original Article Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth The EMBO Journal Article (17 Jun 2002) |
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