Journal article
Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks
Molecular endocrinology (Baltimore, Md.), Vol.29(8), pp.1195-1218
08/2015
DOI: 10.1210/me.2015-1021
PMCID: PMC4517998
PMID: 26181434
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.
Details
- Title: Subtitle
- Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks
- Creators
- Jordy J Hsiao - 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 98195Brandon H Ng - 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 98195Melinda M Smits - 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 98195Harryl D Martinez - 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 98195Rohini J Jasavala - 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 98195Izumi V Hinkson - 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 98195Damian Fermin - 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 98195Jimmy K Eng - 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 98195Alexey I Nesvizhskii - 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 98195Michael E Wright - 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
- Resource Type
- Journal article
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.29(8), pp.1195-1218
- Publisher
- United States
- DOI
- 10.1210/me.2015-1021
- PMID
- 26181434
- PMCID
- PMC4517998
- ISSN
- 0888-8809
- eISSN
- 1944-9917
- Grant note
- R01 GM094231 / NIGMS NIH HHS
- Language
- English
- Date published
- 08/2015
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984025352502771
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