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RNA-seq in the U2OS-AR cell line to identify genes regulated by the androgen receptor

ABSTRACT: RNA-seq in the U2OS-AR cell line to identify genes regulated by the androgen receptor

PROVIDER: PRJEB40608 | ENA |

REPOSITORIES: ENA

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RNA-seq in the U2OS-AR cell line to identify genes regulated by the androgen receptor

Project description:To identify the genes regulated by the androgen receptor (AR), we performed RNA-seq in the U2OS-AR cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for human AR), upon androgen (R1881) or vehicle (DMSO) treatment for 24 hours.

2021-03-09 | E-MTAB-9622 | biostudies-arrayexpress

Glucocorticoid and androgen receptor profiling (ChIP-seq) in U2OS-GR and U2OS-AR cells upon hormone treatment

Project description:We performed ChIP-seq targeting the glucocorticoid receptor (GR) in the U2OS-GR cell line and the androgen receptor (AR) in the U2OS-AR cell line. The cell lines are derived from U2OS ATTC:HTB-96 and stably transfected with an expression construct for either rat GR or human AR, respectively. The U2OS-GR cells were treated with dexamethasone (1 µM) for 90 minutes. The U2OS-AR cells were treated with R1881 (5 nM) for 4 hours.

2021-03-09 | E-MTAB-9616 | biostudies-arrayexpress

ATAC-seq in the U2OS-AR cell line comparing cells treated for 4 hours with 5 nM R1881 to vehicle (DMSO) control-treated cells

Project description:We performed ATAC-seq in the U2OS-AR cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for human AR), upon androgen (R1881) or vehicle (DMSO) treatment for 4 hours.

2021-03-09 | E-MTAB-9606 | biostudies-arrayexpress

Glucocorticoid and androgen receptor profiling (ChIP-seq) in U2OS-GR and U2OS-AR cells upon hormone treatment

Project description:Glucocorticoid and androgen receptor profiling (ChIP-seq) in U2OS-GR and U2OS-AR cells upon hormone treatment

| PRJEB40596 | ENA

Genome-wide analysis of full-length Androgen Receptor (AR) and AR Splice Variant (ARv567es) cistromes

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

GATA2 facilitates steroid receptor coactivator (SRC) recruitment to the androgen receptor (AR) complex

Project description:The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a “first-in-field” approach to target AR expression and function and improve outcomes in CRPC. LNCaP cells were transfected with control siRNA (3), GATA2 siRNA (3) or AR siRNA for 72 hours.

2015-01-21 | E-GEOD-63539 | biostudies-arrayexpress

Androgen Receptor Activity is Regulated Through the Mobilization of Cell Surface Receptor Networks

Project description:The aberrant expression of androgen receptor (AR)-dependent transcriptional programs is a defining pathology of the development and progression of prostate cancers. Transcriptional cofactors that bind AR are critical determinants of prostate tumorigenesis. To gain a deeper understanding of the proteins linked to AR-dependent gene transcription, we performed a DNAaffinity chromatography-based proteomic screen designed to identify proteins involved in ARmediated gene transcription in prostate tumor cells.

2015-09-03 | PXD002596 | Pride

Genome-wide profiling of H3K27ac, H3K4me1, H3K27me3 and H3K9me3 (ChIP-seq) in U2OS-GR and U2OS-AR cells

Project description:We performed ChIP-seq targeting the H3K27ac, H3K4me1, H3K27me3 and H3K9me3 in the U2OS-GR and U2OS-AR cell lines. The cell lines are derived from U2OS ATTC:HTB-96 and stably transfected with an expression construct for either rat GR or human AR, respectively. The U2OS-GR cells were treated with dexamethasone (1 µM) or vehicle (ethanol) for 90 minutes. The U2OS-AR cells were treated with R1881 (5 nM) or vehicle (DMSO) for 4 hours.

2021-03-09 | E-MTAB-9617 | biostudies-arrayexpress

Genome-wide analysis of androgen receptor (AR) SUMOylation effects on gene expression (HEK293).

Project description:Androgen receptor (AR) plays an important regulatory role during prostate cancer development. ARM-bM-^@M-^Ys transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications. To study the role of the AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer and HEK293 cell lines stably expressing wild-type (wt) or SUMOylation site-mutated AR (AR-K386R,K520R). Our genome-wide gene expression analyses reveal that the SUMOylation modulates the AR function in a target gene and pathway selective manner. The transcripts that are differentially regulated by androgen and SUMOylation are linked to cellular movement, cell death, cellular proliferation, cellular development and cell cycle. In line with these data, SUMOylation mutant AR cells proliferate faster and are more sensitive to apoptosis. Moreover, ChIP-seq analyses show that the SUMOylation modulates the chromatin occupancy of AR on many loci in a fashion that parallels with their differential androgen-regulated expression. De novo motif analyses show that other transcription factor-binding motifs are differentially enriched at the wtAR- and the AR-K386R,K520R-preferred genomic binding positions. Taken together, our data indicate that SUMOylation does not simply repress the AR activity, but it regulates ARM-bM-^@M-^Ys interaction with the chromatin and the receptorM-bM-^@M-^Ys target gene selection. Isogenic HEK293 cells stably expressing wild-type AR (wtAR) or SUMOylation-defective AR (AR-K2R) were treated 24 h with 10 nM R1881 or vehicle (EtOH). All conditions were performed in triplicate. The effect on gene expression was assessed by microarray.

2014-07-03 | E-GEOD-54137 | biostudies-arrayexpress

Androgen receptor RIME using LNCaP cells

Project description:Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) was conducted to examine interactome of androgen receptor (AR) in LNCaP cells.

2021-09-10 | PXD024030 | JPOST Repository

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