The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signalling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. While previous studies have focused on ligand-dependent AR signalling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that the AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a distinct gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal. Overall design: LNCaP, C4-2B, or 22RV1 cells were cultured in hormone-free media for 3 days and then treated with ethanol vehicle or DHT (10nM) for 4h or 16h prior to ChIP-seq or RNA-seq assays. For siRNA transfection, cells were transfected with AR siRNA or control siRNA for 3 days prior to RNA-seq assays.
Androgen receptor-mediated downregulation of microRNA-221 and -222 in castration-resistant prostate cancer.
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View SamplesGenome-wide approach to identify the cell-autonomous role of Snf2h in lens fiber cell terminal differentiation. Differential gene expression was analyzed in Snf2h lens-conditional knockout and wildtype newborn mouse eyeballs, with subsequent comparison of this data with the Brg1 lens-conditional knockout mouse eyes expression data (GSE25168).
Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation.
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View SamplesProstate tumors are among the most heterogeneous of cancers, both histologically and clinically. Microarray expression analysis was used to determine whether global biological differences underlie common pathological features of prostate cancer and to identify genes that might anticipate the clinical behavior of this disease. While no expression correlates of age, serum prostate specific antigen (PSA), and measures of local invasion were found, a set of genes was identified that strongly correlated with the state of tumor differentiation as measured by Gleason score. Moreover, a model using gene expression data alone accurately predicted patient outcome following prostatectomy. These results support the notion that the clinical behavior of prostate cancer is linked to underlying gene expression differences that are detectable at the time of diagnosis.
Gene expression correlates of clinical prostate cancer behavior.
Specimen part
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EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.
Cell line, Treatment
View SamplesEZH2 is frequently over-expressed in aggressive and metastatic solid tumors, including castration resistant prostate cancer (CRPC). We sought to determine EZH2-dependent gene expression programmes in prostate cancer progression, and found an intriguing functional switch of EZH2 from a repressor to an activator during CRPC development.
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.
Cell line, Treatment
View SamplesThe androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis Overall design: Gene expresion profiles when LHSAR with overexpressed FOXA1, HOXB13 or FOXA1 and HOXB13 together compared with LacZ control
The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
View SamplesProfiling of gene expression in Vastus Lateralis from female patients before and after GBP surgery and from lean Control
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
View SamplesAndrogen 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.
Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.
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View SamplesIn contrast to the considerable in vitro and in vivo data demonstrating a decrease in cytochrome P450 (CYP) activity in inflammation and infection, clinically, traumatic brain injury (TBI) results in an increase in CYP and UDP glucuronosyltransferases (UGT) activity. The objective of this study was to determine the effects of TBI alone and along with treatment with either erythropoietin (EPO) or anakinra on gene expression of hepatic inflammatory proteins and drug metabolizing enzymes and transporters in a cortical contusion impact (CCI) injury animal model. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h and 7 days post-CCI.
Effect of Traumatic Brain Injury, Erythropoietin, and Anakinra on Hepatic Metabolizing Enzymes and Transporters in an Experimental Rat Model.
Sex, Specimen part, Treatment, Time
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