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  • Original Paper
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Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1

Oncogene volume 21, pages 5609–5618 (2002)Cite this article

Abstract

Members of the ErbB family of receptors have been implicated in regulation of androgen receptor (AR) activity. Ebp1, an ErbB-3 binding protein recently cloned in our laboratory, possesses an LXXLL motif important in mediating interactions with nuclear hormone receptors. Therefore, we sought to determine if Ebp1 could bind AR and influence AR transcriptional activation potential. We demonstrate in this study that Ebp1 bound to AR in vitro and in vivo, and that this binding was increased by androgen treatment. The C terminal 79 amino acids of Ebp1 were sufficient to bind AR. The N terminal domain of AR was responsible for binding Ebp1. Ligand-mediated transcriptional activation of both artificial and natural AR regulated promoters was inhibited by ectopic expression of ebp1 in transient transfection systems. Ebp1 deletion mutants that either lacked the C terminal AR binding region or had a mutated LXXLL motif failed to inhibit AR activated transcription. PSA expression from its endogenous promoter was also decreased in LNCaP prostate cancer cells overexpressing Ebp1. The growth of AR positive LNCaP cells was inhibited by ectopic expression of ebp1, but mutants that failed to repress transcription did not inhibit cell growth. These studies suggest that Ebp1 may play a role in the function of the AR and provide a link between ErbB receptors and the AR.

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Acknowledgements

This work was supported in part by the Susan Komen Foundation and NIH R01 CA76047 and R21 088882-01 (to AW Hamburger). We thank Dr Olli Janne for the androgen responsive reporter gene and AR expression plasmids, and Dr Martin Gleave for the PSA reporter construct.

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Authors and Affiliations

  1. Greenebaum Cancer Center, University of Maryland, Baltimore, 21201, Maryland, MD, USA

    Yuexing Zhang, Xianmin Xia & Anne W Hamburger

  2. Department of Pathology, University of Maryland, Baltimore, 21201, Maryland, MD, USA

    Yuexing Zhang & Anne W Hamburger

  3. Department of Physiology, University of Maryland, Baltimore, 21201, Maryland, MD, USA

    Joseph D Fondell, Qianben Wang & Aiwu Cheng

  4. Department of Surgery, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Michael L Lu

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  1. Yuexing Zhang
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  2. Joseph D Fondell
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Correspondence to Anne W Hamburger.

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Zhang, Y., Fondell, J., Wang, Q. et al. Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1. Oncogene 21, 5609–5618 (2002). https://doi.org/10.1038/sj.onc.1205638

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  • DOI: https://doi.org/10.1038/sj.onc.1205638

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