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 (CSR)-dependent signal transduction pathways. Further experimentation demonstrated that components of the tumor necrosis factor (TNF), transforming growth factor-beta (TGF-β), interleukin receptor (IL-R), and epidermal growth factor (EGF) signaling pathways modulated AR-dependent gene transcription and androgen-dependent proliferation in prostate-tumor cells. Collectively, our proteomic dataset demonstrates that the CSR- 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.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 August 2015.
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