title: Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks.
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.
authors.affiliation: 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.
authors.forename: Jordy J
authors.initials: JJ
authors.lastname: Hsiao
authors.affiliation: 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.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Ng
authors.affiliation: 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.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: 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.
authors.forename: Harryl D
authors.initials: HD
authors.lastname: Martinez
authors.affiliation: 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.
authors.forename: Rohini J
authors.initials: RJ
authors.lastname: Jasavala
authors.affiliation: 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.
authors.forename: Izumi V
authors.initials: IV
authors.lastname: Hinkson
authors.affiliation: 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.
authors.forename: Damian
authors.initials: D
authors.lastname: Fermin
authors.affiliation: 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.
authors.forename: Jimmy K
authors.initials: JK
authors.lastname: Eng
authors.affiliation: 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.
authors.forename: Alexey I
authors.initials: AI
authors.lastname: Nesvizhskii
authors.affiliation: 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.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wright
mesh_terms: D000728:Androgens / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D019295:Computational Biology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C410798:AR protein, human; D000728:Androgens; D016207:Cytokines; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D004247:DNA