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E-GEOD-40050 - Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions

Status
Released on 2 October 2012, last updated on 3 May 2014
Organism
Homo sapiens
Samples (35)
Protocols (39)
Description
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. 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.
Experiment types
ChIP-seq, RNA-seq of coding RNA, RNA-seq of non coding RNA 
Contacts
Dali Zheng, John R Edwards, Keith F Decker, Li Jia, Tamara Bowman, Yuhong He
Citation
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-40050.idf.txt
Sample and data relationshipE-GEOD-40050.sdrf.txt
Processed data (28)Click to browse processed data
Additional data (1)E-GEOD-40050.additional.1.zip
Links