Project description:This SuperSeries is composed of the following subset Series: GSE4453: Androgen receptor coregulators baseline comparisons GSE4454: Androgen receptor-coregulators hormone responsiveness LNCaP / GSF Refer to individual Series
Project description:To decipher the contribution of coregulators to androgen receptor target gene expression, effect of siRNA-mediated silencing of 18 clinically relevant coregulators on bona fide androgen receptor target gene expression was studied.
Project description:The androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as androgen receptor trapped clone-27 (ART-27). The impact of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are upregulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low. Keywords: LNCaP, cell type comparison, UXT, ART-27, androgen receptor, R1881, AR, androgen-regulated gene expression, prostate cancer
Project description:Androgen receptor (AR) is a master transcription factor that drives prostate cancer (PCa) development and progression. Alterations in the expression or activity of AR coregulators significantly impact the disease's outcome. To identify all the essential components of the AR coregulator complex, we utilized a proteomic approach called rapid immunoprecipitation of endogenous proteins (RIME) to systematically identify all coregulator proteins of the AR interactome in PCa cells.
Project description:The androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as androgen receptor trapped clone-27 (ART-27). The impact of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are upregulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low. Experiment Overall Design: Steroid-deprived LNCaP cells were transfected with control or ART-27 siRNA and stimulated with ethanol vehicle or 10 nM R1881 for 18 hrs. 8 samples, 4 conditions, 2 replicates per condition.
Project description:This SuperSeries is composed of the following subset Series: GSE30622: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [Expression Array] GSE30623: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [ChIP_seq, DHS_seq] Refer to individual Series
Project description:Treatment of prostate cancer confronts resistance to androgen receptor (AR)-targeted therapies. AR-associated coregulators and chromatin proteins hold a great potential for novel therapy targets. Here, we employed a powerful chromatin-directed proteomics approach termed ChIP-SICAP to uncover the composition of chromatin protein network, the chromatome, around endogenous AR in castration resistant prostate cancer (CRPC) cells. In addition to several expected AR coregulators, the chromatome contained many nuclear proteins not previously associated with the AR. In the context of androgen signaling in CRPC cells, we further investigated the role of a known AR-associated protein, a chromatin remodeler SMARCA4 and that of SIM2, a transcription factor without a previous association with AR. To understand their role in chromatin accessibility and AR target gene expression, we integrated data from ChIP-seq, RNA-seq, ATAC-seq and functional experiments. Despite the wide co-occurrence of SMARCA4 and AR on chromatin, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, especially those involved in cell morphogenetic changes in epithelial-mesenchymal transition. The depletion also inhibited the CRPC cell growth, validating its functional role in CRPC cells. Although silencing of SIM2 reduced chromatin accessibility similarly, it affected the expression of a much larger group of androgen-regulated genes, including those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of CRPC cells and tumor size in chick embryo chorioallantoic membrane assay, further emphasizing the importance of SIM2 in CRPC cells and pointing to the functional relevance of this potential prostate cancer biomarker in CRPC cells. Overall, the chromatome of AR identified in this work is an important resource for the field focusing on this important drug target.
Project description:Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) was conducted to examine interactome of androgen receptor (AR) in LNCaP cells.