Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA253024 | ENA |
REPOSITORIES: ENA
Similar Datasets
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 aim of the study is to identify AR target gens in LNCaP cells 5 samples corresponding to LSD1 K114me2 or CHD1 genome-binding in DHT-treated and control LNCaP cells. 6 samples corresponding to LSD1 K114me2 or CHD1 genome-binding in LNCaP cells knocked-down for LSD1 or CHD1 and treated with DHT.
2015-12-07 | E-GEOD-64528 | biostudies-arrayexpress
Project description:Analyze the transcriptomic changes of LNCaP upon DMSO, DHT, Enzalutamide(ENZ), ET516 treatment. The DHT treatment induced robust androgen receptor (AR) signaling up-regulation, wheras ENZ and ET516 can significantly restore DHT-induced AR signaling changes.
2021-10-05 | GSE185223 | 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:Testing the hormonal response of ZR-75-1 cells to estrogen, androgens, and a combination of both homones, with view determining the crosstalk between the transcriptional programs mediated by these hormones in breast cancer cells, and comparison with matched ChIP sequencing data for AR and ERalpha. Data analysis demonstrated reciprocal interference between 5α-dihydrotestosterone (DHT)- and estradiol (E2)-induced transcriptional programs. Specifically, regulation of 26% of E2 and 15% of DHT target genes was significantly affected by cotreatment with the other hormone, in the majority of cases (78-83%) antagonistically. Pathway analysis suggested that DHT co-treatment, for example, depleted E2-regulted pathways in cell survival and proliferation. Total RNA was extractd from luminal-like breast cancer ZR-75-1 cells in quadruplicate after treatment for 16h with 10nM of E2, DHT or E2+DHT.
2012-10-03 | E-GEOD-38132 | 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:Testing the hormonal response of ZR-75-1 cells to estrogen, androgens, and a combination of both homones, with view determining the crosstalk between the transcriptional programs mediated by these hormones in breast cancer cells, and comparison with matched ChIP sequencing data for AR and ERalpha. Data analysis demonstrated reciprocal interference between 5α-dihydrotestosterone (DHT)- and estradiol (E2)-induced transcriptional programs. Specifically, regulation of 26% of E2 and 15% of DHT target genes was significantly affected by cotreatment with the other hormone, in the majority of cases (78-83%) antagonistically. Pathway analysis suggested that DHT co-treatment, for example, depleted E2-regulted pathways in cell survival and proliferation.
2012-10-03 | GSE38132 | GEO
Project description:This study was undertaken to compare efficacy of MJC13 and the classic AR antagonist flutamide. Both compounds modulate endogenous AR target gene expression in Prostate cancer cells in a similar fashion despite different mechanisms of action. LNCaP cells were seeded within 6-well dishes at density of 1 à 100,000 within RPMI 1640 media supplemented with L-glutamine and 10% fetal bovine serum (FBS), day 2 the media replaced with RPMI 1640 media supplemented with L-glutamine and 10% charcoal-stripped FBS, day 3 the cells were treated with DMSO (control), 10nM DHT, 1μM Flutamide, 1μM Flutamide + 10nM DHT, 30μM MJC13, or 30μM MJC13 + 10nM DHT for 24 hours, after which total RNA was isolated.
2015-12-31 | E-GEOD-65562 | biostudies-arrayexpress