Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks
| Autor: | Jimmy K. Eng, Alexey I. Nesvizhskii, Harryl D. Martinez, Jordy J. Hsiao, Rohini J. Jasavala, Brandon H. Ng, Melinda M. Smits, Damian Fermin, Michael E. Wright, Izumi V. Hinkson |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Proteomics Transcription Genetic Receptors Cell Surface Biology Real-Time Polymerase Chain Reaction Bioinformatics Mass Spectrometry Endocrinology Transcription (biology) Cell surface receptor Epidermal growth factor Cell Line Tumor Humans 5-HT5A receptor RNA Small Interfering Molecular Biology Original Research Binding Sites General transcription factor Gene Expression Profiling Cell Membrane GATA3 Computational Biology Prostatic Neoplasms DNA General Medicine Cell biology Gene Expression Regulation Neoplastic Androgen receptor Receptors Androgen Mutation Androgens Disease Progression Cytokines Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Molecular Endocrinology. 29:1195-1218 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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