Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA324293 | ENA |
REPOSITORIES: ENA
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Project description:Identification of DHT induced cell cycle dependent trascriptome and AR binding events
| PRJNA324290 | ENA
Project description:Microarray experiments were carried out to ascertain whether TOP2β is required for DHT induced androgen receptor target gene expression. We investigated the effect of pharmacological inhibition or RNA interference-mediated depletion of TOP2β on gene expression in androgen-dependent LNCaP prostate cancer cells. Analysis of gene expression in LNCaP cells under various conditions including serum starvation, DHT treatment, and DHT treatment combined with TOPO2B pharmacological inhibitors (Merbarone and Etoposide) and TOPO2B-shRNA knockdown.
2010-07-29 | E-GEOD-19445 | biostudies-arrayexpress
Project description:Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. We investigated AR-induced gene expression in prostate cancer cells LNCaP and abl by transfecting siAR / siControl or treating cells with androgen (DHT) over a time course. Experiment Overall Design: We hybridized RNA to Affymetrix human genome U133 plus 2.0 arrays.
2009-08-07 | E-GEOD-11428 | biostudies-arrayexpress
Project description:Identification of cell cycle regulated, DHT induced AR binding events
| PRJNA324292 | ENA
Project description:Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. We investigated AR-induced gene expression in prostate cancer cells LNCaP and abl by transfecting siAR / siControl or treating cells with androgen (DHT) over a time course. Keywords: siRNA transfection and androgen stimulation time course
2009-07-25 | GSE11428 | GEO
Project description:Purpose: To evalute the antagonistic effects of White Button Mushroom/WBM extract on AR signaling in human prostate cance cells. Methods: LNCaP cells were treated with 1 nM DHT, with or without WBM extract (3 μL/mL), for 48h, in triplicates, and total RNA was isolated and sequenced. Results: We identified 155 up-regulated genes (Fold-change ≥ 2, p<0.05) versus 185 down-regulated genes (Fold-change ≤ 0.5, p<0.05). Conclusion: White Button Mushroom suppressed androgen respsonive genens and cell cycle division genes Collectively, these results suggest that WBM extract affects prostate cancer by interrupting AR-dependent cell cycle division and DNA replication.
2021-01-01 | GSE160723 | GEO
Project description:The discovery that enhancers are regulated transcription units, encoding eRNAs, has raised new questions about the mechanisms of their activation. Here, we report an unexpected molecular mechanism that underlies ligand-dependent enhancer activation, based on DNA nicking to relieve torsional stress from eRNA synthesis. Using dihydrotestosterone (DHT)-induced binding of androgen receptor (AR) to prostate cancer cell enhancers as a model, we show rapid recruitment, within minutes, of DNA topoisomerase I (TOP1) to a large cohort of AR-regulated enhancers. Furthermore, we show that the DNA nicking activity of TOP1 is a prerequisite for robust eRNA synthesis and enhancer activation and is kinetically accompanied by the recruitment of ATR and the MRN complex, followed by additional components of DNA damage repair machinery to the AR-regulated enhancers. Together, our studies reveal a linkage between eRNA synthesis and ligand-dependent TOP1-mediated nicking - a strategy exerting quantitative effects on eRNA expression in regulating AR-bound enhancer-dependent transcriptional programs. Genome-wide binding analysis of AR, TOP1, MRE11 in prostate cancer cell line LNCaP with or without 5alpha-dihydrotestosterone (DHT) treatment. Nascent RNA analysis by global nuclear run-on (GRO-seq) in LNCaP cells transfected with siRNA with or without DHT treatment. Distribution of transcriptionally engaged RNA Pol II in LNCaP cells with or without DHT treatment by precision nuclear run-on and sequencing (PRO-seq).
2015-01-22 | E-GEOD-63202 | biostudies-arrayexpress
Project description:Microarray experiments were carried out to ascertain whether TOP2β is required for DHT induced androgen receptor target gene expression. We investigated the effect of pharmacological inhibition or RNA interference-mediated depletion of TOP2β on gene expression in androgen-dependent LNCaP prostate cancer cells.
2010-07-04 | GSE19445 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE4299: Resveratrol-Induced Gene Expression Profiles in Human Prostate Cancer Cells GSE4300: Androgen arrays for Resveratrol-Induced Gene Expression Profiles in Human Prostate Cancer Abstract: OBJECTIVE: The transhydroxystilbene resveratrol is found at high levels in red wine and grapes, and red wine consumption may be inversely associated with prostate cancer risk. To gain insights into the possible mechanisms of action of resveratrol in human prostate cancer, we did DNA microarray analysis of the temporal transcriptional program induced by treatment of the human prostate cancer cell line LNCaP with resveratrol. METHODS: Spotted DNA microarrays containing over 42,000 elements were used to obtain a global view of the effects of resveratrol on gene expression. Prostate-specific antigen (PSA) and androgen receptor (AR) expression were determined by Northern blot and immunoblot analyses. Cell proliferation was determined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and cell cycle analysis by flow cytometry. RESULTS: We observed time-dependent expression changes in >1,600 transcripts as early as 6 hours after treatment with resveratrol. Most striking was the modulation of a number of important genes in the androgen pathway including PSA and AR. Resveratrol also down-regulated expression of cell cycle and proliferation-specific genes involved in all phases of the cell cycle, induced negative regulators of proliferation, caused accumulation of cells at the sub-G1 and S phases of the cell cycle, and inhibited cell proliferation in a time- and dose-dependent manner. CONCLUSION: Resveratrol produces gene expression changes in the androgen axis and cell cycle regulators that may underlie its putative anticancer activities in prostate cancer. Refer to individual Series
2006-03-07 | E-GEOD-4399 | biostudies-arrayexpress
Project description:While thousands of long non-coding RNAs (lncRNAs) are expressed in higher eukaryotes, the potential regulatory roles of lncRNAs in regulated gene transcription programs remain rather poorly understood. Here, we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 and PCGEM1, bind successively to the androgen receptor (AR) and strongly enhance both ligand-dependent and ligand-independent AR-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the C-terminally acetylated AR on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM, to the N-terminally methylated AR. Unexpectedly, recognition of the H3K4me3 promoter mark by the PHD finger-domain of Pygopus2, recruited by PCGEM1, proves to enhance selective looping of AR-bound enhancers to target gene promoters in these cells, revealing a novel aspect of ligand-induced enhancer-promoter interactions. In “resistant” prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for the robust activation of both truncated and full length AR, causing DHT-independent activation of the AR transcriptional program and cell proliferation. Conditionally-expressed short hairpin RNA (shRNA)-mediated targeting of these lncRNAs in these resistant cancer cell lines strongly suppressed xenograft growth in vivo. Together, these results suggest that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumors. Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq); after knocking down PYGO2 LNCaP cells were grown to 30-50% confluence and siRNA/ASO transfections were carried out using Lipofectamine 2000 (Invitrogen) according to the manufacturer’s instructions. Control samples were transfected with scramble ASO and control siRNA, respectively. On the following day of transfection, the cells were cultured in UltraCULTURE (Phenol red free) + 5% Charcoal Dextran Stripped (CDS) serum for 48 hours. For androgen induction, we treat cells with DHT from a 100 uM stock in 70% ethanol to a final concentration of 100 nM for 1 hour Control siRNA, -DHT Control siRNA, +DHT Pygo2 siRNA, -DHT Pygo2 siRNA, +DHT
2013-08-15 | E-GEOD-47805 | biostudies-arrayexpress