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Mol Endocrinol. 2015 Aug;29(8):1195-218. doi: 10.1210/me.2015-1021. Epub 2015 Jul 16.

Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks.

Author information

1
Department of Molecular Physiology and Biophysics (J.J.H., B.H.N., M.M.S., H.D.M., M.E.W.), Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242; Department of Pharmacology (H.D.M., R.J.J., I.V.H., M.E.W.), School of Medicine and Genome Center, University of California, Davis, California 95616; Departments of Pathology and Computational Medicine and Bioinformatics (D.F., A.I.N.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Genome Sciences (J.K.E.), University of Washington, Seattle, Washington 98195.

Abstract

The aberrant expression of androgen receptor (AR)-dependent transcriptional programs is a defining pathology of the development and progression of prostate cancers. Transcriptional cofactors that bind AR are critical determinants of prostate tumorigenesis. To gain a deeper understanding of the proteins linked to AR-dependent gene transcription, we performed a DNA-affinity chromatography-based proteomic screen designed to identify proteins involved in AR-mediated gene transcription in prostate tumor cells. Functional experiments validated the coregulator roles of known AR-binding proteins in AR-mediated transcription in prostate tumor cells. More importantly, novel coregulatory functions were detected in components of well-established cell surface receptor-dependent signal transduction pathways. Further experimentation demonstrated that components of the TNF, TGF-β, IL receptor, and epidermal growth factor signaling pathways modulated AR-dependent gene transcription and androgen-dependent proliferation in prostate tumor cells. Collectively, our proteomic dataset demonstrates that the cell surface receptor- and AR-dependent pathways are highly integrated, and provides a molecular framework for understanding how disparate signal-transduction pathways can influence AR-dependent transcriptional programs linked to the development and progression of human prostate cancers.

PMID:
26181434
PMCID:
PMC4517998
DOI:
10.1210/me.2015-1021
[Indexed for MEDLINE]
Free PMC Article

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