Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Olli Jänne
PROVIDER: E-GEOD-30624 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We report the dual role of FoxA1 in androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell line LNCaP-1F5 using ChIP-sequencing. Depletion of FoxA1 reprograms both androgen and glucocorticoid receptor recruitment and subsequent gene expression. The ChIP-seq has been performed using AR, FoxA1, GR, H3K4me2 antibodies. We have also mapped the DNaseI-hypersensitive sites (DHS) using deep sequencing. Examination of AR, FoxA1, GR, H3K4me2 binding sites and DHS sites in parental and FoxA1 depleted LNCaP-1F5 cells.
2011-09-14 | E-GEOD-30623 | biostudies-arrayexpress
Project description:We report the dual role of FoxA1 in androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell line LNCaP-1F5 using ChIP-sequencing. Depletion of FoxA1 reprograms both androgen and glucocorticoid receptor recruitment and subsequent gene expression. The ChIP-seq has been performed using AR, FoxA1, GR, H3K4me2 antibodies. We have also mapped the DNaseI-hypersensitive sites (DHS) using deep sequencing. LNCaP-1F5 cells were depleted of FoxA1 using siRNAs. Parental cells and FoxA1 depleted cells (siFoxA1) were treated with vehicle or 100 nM DHT or (100 nM DEX) for 24 hours followed by RNA isolation and hybridization to Illumina arrays. All the experiments have been performed in biological duplicates. Parental cells treated with DHT (or DEX) were analyzed for differentially expressed genes compared to vehicle treated parental cells. Similarly siFoxA1 cells treated with DHT (or DEX) were analyzed for differentially expressed genes compared to vehicle treated siFoxA1 cells.
2011-09-13 | E-GEOD-30622 | 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 (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:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-05 | E-GEOD-39880 | 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:The androgen receptor (AR) mediates the action of androgens by binding to androgen-responsive elements (AREs) and subsequently regulating target genes involved in prostate carcinogenesis. The precise locations, true nature, and functional roles of AREs in human prostate cancer are still unknown. Here we redefine AREs by motif-resolution AR chromatin immunoprecipitation-exonuclease (ChIP-exo) assay in human prostate cancer cells and tumors. Surprisingly, we find that, in addition to canonical full-length AREs and half-site-like AREs, a significant portion of the four redefined ARE categories comprises non-canonical full-length AREs. The redefined AREs in enhanced AR binding regions in prostate tumors versus paired non-malignant adjacent tissues regulate a prostate cancer-relevant gene network not only centered on AR, but more interestingly, on novel AR target genes mTOR, BIRC5 and BCL2L1 involved in prostate cancer cell growth and survival. The precise redefinition of AREs has important implications for understanding how AR contributes to prostate carcinogenesis. FOXA1 ChIP-exo
2015-01-01 | E-GEOD-43678 | 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:GATA2 and FOXA1 are pioneering factors for Androgen Receptor (AR) in prostate cancer cells. Less is known about their role in benign epithelial prostate cells. We investigated if they had the ability to induce differentiation in an undifferentiated prostatic context. Benign basal-like prostate epithelial cells 957E/hTERT-AR cells (a gift from John T. Isaacs lab, Johns Hopkins, MD, USA) were transduced with LentiORF RFP control lentiviral particles. The 957E/hTERT-AR-RFP cells were then transduced with GATA2 and FOXA1 lentiviral particles, and we called the new cell lines hTERT/AR-GATA2 and hTERT/AR-FOXA1, respectively. hTERT/AR-GATA2 is a stable selected cell line and treated with 1 nM anabolic steroids, R1881, or ethanol (ET-OH) for 48 hrs. 957E/hTERT/AR-FOXA1 is a transient cell line, because FOXA1 protein is quickly lost. Twenty four hours post transduction with FOXA1 lentivral particles, 1 nM androgen R1881 or ethanol (ET-OH) were added at time for medium exchange and further treated for 24 hours. GATA-2 and FOXA1 ability to induce differentiation was assessed.
2018-12-01 | E-MTAB-5121 | 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. MDA-MB-453 breast cancer cells were transfected with control of MYC siRNA for 48 h, followed by treatment with 10nM DHT or vehicle for 6 h. The cells were subjected to mRNA purification and library praparation for RNA-seq on Illumina HiSeq2000 platform.
2013-03-16 | E-GEOD-45202 | biostudies-arrayexpress
Project description:Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction. Examination of AR, VDR, and FOXA1 binding in LNCaP cells, in biological replicates
2015-08-01 | E-GEOD-64656 | biostudies-arrayexpress