GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE72714 Query DataSets for GSE72714
Status Public on Mar 08, 2016
Title ROR-γ drives androgen-receptor expression and represents a therapeutic target in castration-resistant prostate cancer
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor–related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR–ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.
Overall design A total of 16 samples were analyzed in this study. The study included one cell line C4-2B. C4-2B cells were cultured in medium containing vehicle control or SR2211 (5 µM) for 24 hours, cells then were collected for ChIP seq assay
Contributor(s) Chen H, Wang J
Citation(s) 27019329
Submission date Sep 04, 2015
Last update date May 15, 2019
Contact name Junjian Wang
Phone 9167343221
Organization name UC Davis
Department Biochemistry and molecular medicine
Street address rm1204, Res3, 4645 2nd Ave
City Sacramento
State/province california
ZIP/Postal code 95817
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (16)
GSM1868862 2nd time C4-2B vehicle AR chip seq
GSM1868863 2nd time C4-2B SR2211 AR chip seq
GSM1868864 2nd time C4-2B vehicle Input chip seq
BioProject PRJNA294735
SRA SRP063334

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72714_RAW.tar 7.2 Gb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap