Identification of cell cycle regulated, DHT induced AR binding events
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE82202 | GEO | 2016/10/05
SECONDARY ACCESSION(S): PRJNA324292
REPOSITORIES: GEO
Similar Datasets
Project description:The molecular drivers for the AR signaling reprogramming in castration-resistant prostate cancer remain to be determined. In this study, we hypothesize that increased AR expression in conjunction with lower-level androgens, which is a typical condition in prostate cancer cells receiving androgen deprivation therapy, is a major driving force of the reprogramming. To test this, we used LNCaP model with inducible overexpression of AR to examine the acute effects of AR overexpression stimulated by low-dose DHT (0.1nM) on AR cistrome.
2022-11-21 | GSE211639 | GEO
Project description:The majority of breast cancer subtypes express androgen receptor (AR) in addition to estrogen receptor α (ERα). Depending on the breast cancer subtype androgen signaling has either stimulatory or inhibitory roles in breast cancer cell growth. We have mapped AR cistrome in ERα negative human molecular apocrine breast cancer MDA-MB453 cells and analyzed it in relation to the androgen-regulated transcriptome in the same cells. We have also examined the effect of silencing of the coregulator SUMO ligase PIAS1 on the androgen-regulated transcriptome and AR cistrome in MDA-MB453 cells. Our results show that the MDA-MB453 cells share with VCaP prostate cancer cells a core AR cistrome and target gene signature linked to cancer cell growth and that PIAS1 acts as an AR target gene-selective coregulator in MDA-MB453 cells. MDA-MB453 cells were transfected with control siRNA (siNON) or PIAS1 siRNA (siPIAS1) for 72 h and treated 16 h with 10 nM R1881 or vehicle (ethanol). Total RNA was isolated and biological triplicate samples were analyzed by microarray.
2016-07-18 | E-GEOD-70162 | biostudies-arrayexpress
Project description:The majority of breast cancer subtypes express androgen receptor (AR) in addition to estrogen receptor α (ERα). Depending on the breast cancer subtype androgen signaling has either stimulatory or inhibitory roles in breast cancer cell growth. We have mapped AR cistrome in ERα negative human molecular apocrine breast cancer MDA-MB453 cells and analyzed it in relation to the androgen-regulated transcriptome in the same cells. We have also examined the effect of silencing of the coregulator SUMO ligase PIAS1 on the androgen-regulated transcriptome and AR cistrome in MDA-MB453 cells. Our results show that the MDA-MB453 cells share with VCaP prostate cancer cells a core AR cistrome and target gene signature linked to cancer cell growth and that PIAS1 acts as an AR target gene-selective coregulator in MDA-MB453 cells.
2016-07-18 | GSE70162 | GEO
Project description:Androgen Receptor (AR) variants (AR-V) drive prostate cancer (PCa) resistance to first and second-generation therapies targeting endocrine regulation of AR. To understand the sets of genomic targets of full-length AR vs. AR-Vs, we conducted genome-wide ChIP-seq using isogenic pairs of genome engineering cell lines expressing either ARv567es (R1-D567) or full-length AR (R1-AD1). Our data demonstrate that androgen-activated full-length AR and AR-Vs both bind to similar genomic targets, which are enriched for high affinity androgen response elements (AREs). Overall, this study demonstrates that AR-Vs restore the broad AR cistrome that is otherwise lost during endocrine-targeted therapy.
2015-03-13 | GSE61838 | GEO
Project description:We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)M-NM-1, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERM-NM-1, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells. Total RNAs from the LNCaP cells transfected with control siRNA (siCT) or siRNA for AR (siAR) transfected LNCaP cells before 24 hr followed by exposed to 10-7M of DHT, E2 or R5020 exposure for another 24 h, respectively, were used.
2014-06-19 | E-GEOD-58615 | biostudies-arrayexpress
Project description:We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)α, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERα, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells.
2014-06-19 | GSE58615 | GEO
Project description:The major pioneer factor activity of FOXA1 in PCa is to facilitate AR recruitment to androgen-regulated enhancers. Therefore, we hypothesized that the decreased FOXA1 binding and enhancer availability by LSD1 inhibition may result in the impairment of subsequent AR recruitment to enhancers. To globally test this hypothesis, we performed AR ChIP-seq in LNCaP cells treated with an LSD1 inhibitors. Consistent with previous reports, DHT treatment can dramatically induce AR binding to chromatin. Significantly, LSD1 inhibitor treatment in presence of DHT stimulation markedly decreased the total number of AR binding peaks and their intensity. We further assessed the impact of LSD1 inhibition on overall AR transcriptional output using RNA-seq data.
2019-09-29 | GSE114266 | GEO
Project description:We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate (CPA), mifepristone (RU486) and bicalutamide (Bica) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies. Examination of AR and GR binding sites in LNCaP-1F5 and VCaP cells in presence of DHT and Dex respectively. Further analysis of AR binding sites in LNCaP-1F5 cells treated with partial agonist/antagonists, CPA, RU486 and Bica. Additionally RNA Pol II mapping is performed in cells treated with DHT and Dex.
2013-02-05 | E-GEOD-39879 | biostudies-arrayexpress
Project description:We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate and mifepristone (RU486) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies. Expression profiling by microarray of LNCaP-1F5 cells treated with vehicle, 100 nM 5a-dihydrotestosterone (DHT), 100 nM dexamethasone (Dex), 1000 nM cyproterone acetate (CPA), 100 nM mifepristone (RU486) and combination of 100 nM DHT,100 nM Dex for 24 hours.
2013-02-05 | E-GEOD-39654 | biostudies-arrayexpress
Project description:We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate and mifepristone (RU486) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies.
2013-02-05 | GSE39654 | GEO