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Series GSE40050 Query DataSets for GSE40050
Status Public on Oct 02, 2012
Title Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Summary 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.
Contributor(s) Decker KF, Zheng D, He Y, Bowman T, Edwards JR, Jia L
Citation(s) 23019221, 28886115
Submission date Aug 10, 2012
Last update date Jun 26, 2019
Contact name Keith F Decker
Organization name Washington University School of Medicine
Department Internal Medicine
Lab Li Jia
Street address 660 S. Euclid Ave, Campus Box 8220
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (35)
GSM984368 C42B vehicle 1
GSM984369 C42B vehicle 2
GSM984370 C42B treated 1
BioProject PRJNA172760
SRA SRP014809

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Supplementary file Size Download File type/resource
GSE40050_RAW.tar 7.5 Gb (http)(custom) TAR (of BEDGRAPH)
GSE40050_RNASEQ_RAW_COUNT_TABLE.txt.gz 349.5 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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