Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA139941 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional profiling of RWPE-1 cells stably expressing human androgen receptor (as described in Altintas et al., Mol Cell Endocrinol 2011) treated with a non-metabolisable androgen, R1881 RWPE-1-AR cells were treated with R1881 during 3h or 24h and compared to control not treated cells. Three independent cell culture experiments for each treatment condition (vehicle or R1881 for 3h and 24h).
2011-05-12 | E-GEOD-29232 | biostudies-arrayexpress
Project description:Androgen signaling through the androgen receptor (AR) regulates multiple pathways in both normal and prostate cancer cells. Androgen regulates diverse aspects of the AR life cycle, including its post-translational modification, but understanding how specific modifications influence AR activity has been mostly elusive. Here, we show that androgen regulates AR through a pathway mediated by the mono-ADP ribosyltransferase, Parp7. We show that Parp7 ADP-ribosylates AR on multiple cysteines, and that a subset of these sites mediates agonist-specific recruitment of the E3 ligase Dtx3L/Parp9. Tandem macrodomains in Parp9 selectively recognize ADP ribosylated AR, and Dtx3L/Parp9 affects expression of a subset of AR-regulated genes. Parp7, ADP-ribosylation of AR, and AR-Dtx3L/Parp9 complex assembly are inhibited by 60 Olaparib, a compound used clinically to inhibit poly-ADP-ribosyltransferases Parp1/2. Our study reveals the components of a new androgen signaling axis that uses a writer and reader of ADP-ribosylation to modulate AR activity.
2021-04-23 | PXD025195 | Pride
Project description:Androgen signaling through the androgen receptor (AR) regulates multiple pathways in both normal and prostate cancer cells. Androgen regulates diverse aspects of the AR life cycle, including its post-translational modification, but understanding how specific modifications influence AR activity has been mostly elusive. Here, we show that androgen regulates AR through a pathway mediated by the mono-ADP ribosyltransferase, Parp7. We show that Parp7 ADP-ribosylates AR on multiple cysteines, and that a subset of these sites mediates agonist-specific recruitment of the E3 ligase Dtx3L/Parp9. Tandem macrodomains in Parp9 selectively recognize ADP ribosylated AR, and Dtx3L/Parp9 affects expression of a subset of AR-regulated genes. Parp7, ADP-ribosylation of AR, and AR-Dtx3L/Parp9 complex assembly are inhibited by 60 Olaparib, a compound used clinically to inhibit poly-ADP-ribosyltransferases Parp1/2. Our study reveals the components of a new androgen signaling axis that uses a writer and reader of ADP-ribosylation to modulate AR activity.
2021-05-28 | PXD018811 | Pride
Project description:Fine mapping of androgen regulated genes in LNCaP cells
| PRJNA121563 | ENA
Project description:Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men and is the third cause of cancer mortality. PCa initiation and growth is driven by the androgen receptor (AR). AR is activated by androgens such as testosterone and controls prostatic cell proliferation and survival. We sought to characterize global AR signalling networks. We performed BioID proximity labeling proteomics in androgen-dependent LAPC4 cells to delineate AR protein interaction networks. We report the identification of 32 AR associated proteins in non-stimulated cells. Strikingly, the AR signalling network increased to 183 and 201 proteins, upon 24h or 72h androgenic stimulation, respectively. Among this group, we identified 215 proteins that were not previously reported as AR interactors. Interestingly, these AR associated proteins were previously reported to be involved in DNA metabolism, RNA processing and RNA polymerase II transcription. Moreover, we identified 44 transcription factors, such as the Krüppel-like factor 4 (KLF4), which was specifically revealed in androgen-stimulated cells. We determined that KLF4 acts as a repressor of AR target genes transcription in PCa cells. Taken together, our data report the largest high-confidence proximity networks for AR in PCa cells.
2021-03-01 | PXD011974 | Pride
Project description:We investigated the composition of chromatin protein network around endogenous androgen receptor (AR) in VCaP castration resistant prostate cancer cells using recently developed chromatin-directed proteomic approach called ChIP-SICAP . The androgen-induced AR chromatin protein network contained expected TFs, e.g. HOXB13, chromatin remodeling proteins, e.g. SMARCA4, and several novel candidates not previously associated with AR, e.g. prostate cancer biomarker SIM2. Based on these findings, the role of SMARCA4 and SIM2 was further characterized at AR chromatin domains . Silencing of SIM2 altered chromatin accessibility at a similar number of AR-binding sites as SMARCA4, an established ATPase subunit of the BAF chromatin remodeling complex, often aberrantly expressed in prostate cancer. Despite the wide co-occurrence on chromatin of SMARCA4 and AR, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, in particular those involved in cell morphogenetic changes in epithelial-mesenchymal transition. Silencing of SIM2, in turn, affected the expression of a much larger group of androgen-regulated genes, e.g. those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of VCaP cells and tumor size in chick embryo chorioallantoic membrane assay, further suggesting the importance of SIM2 in the regulation prostate cancer cells.
2021-06-17 | PXD025193 | Pride
Project description:The spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. Here we identified the cistrome and transcriptome landscape of AR-Vs in CRPC cell lines and determine the clinical significance of AR variants regulated gene.The AR variants binding sites can be identified in 22Rv1 cell line in the absence of androgen. Knocking down full-length AR (AR-FL) doesn't affect AR-Vs binding sites in genome-wide. A set of genes were identified to be regulated uniquely by AR-Vs, but not by AR-FL in androgen-depleted condition. Integrated analysis showed that some genes may be modulated by AR-Vs directly. Unsupervised clustering analysis demonstrated that AR variants gene signature can separate not only the benign and malignant prostate tissue, but also the localized prostate cancer and metastatic CRPC specimens. Some genes modulated uniquely by AR variants were also identified to correlate with the Gleason Pattern of prostate cancer and PSA failure. We conclude that AR spliced variants bind to DNA independent of full-length AR, and can modulate a unique set of genes which is not regulated by full-length AR in the absence of androgen. AR variants gene signature correlate with CRPC and prostate cnacer disease progress. Androgen receptor (AR) binding sites in human prostate cancer 22Rv1 cell lines were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
2014-09-10 | E-GEOD-58478 | biostudies-arrayexpress
Project description:Androgen-stimulated growth of the molecular apocrine breast cancer is mediated by an androgen receptor (AR)-regulated transcriptional program. Through profiling the genomic licalizations of AR and its co-regulators FOXA1 and TCF7L2 in MDA-MB-453 breast cancer cells, we revealed the molecular details of the AR-centered regulatory network. We further identified that c-MYC is a key downstream target co-regulated by AR, FOXA1 and TCF7L2, and reinforces the transctiopnal activation of androgen-responsive genes in this subtype of breast cancers. AR and FOXA1 ChIP-seq were performed in MDA-MB-453 breast cancer cells with treatment of 5a-dihydrotestosterone (DHT) for 16 h. TCF7L2 ChIP-seq was performed in MDA-MB-453 cells treated with vehicle or DHT for 16 h, respectively. MYC ChIP-seq was performed in MDA-MB-453 cells following 6 h DHT stimulation.
2013-03-16 | E-GEOD-45201 | biostudies-arrayexpress
Project description:Identification of PURPL regulated genes in HCT116 cells
| PRJNA314881 | ENA
Project description:Identification of CEBPD regulated genes in MCF7 cells
| PRJNA285959 | ENA