GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE120680 Query DataSets for GSE120680
Status Public on Feb 27, 2019
Title GREB1 amplifies androgen receptor output in prostate cancer and contributes to antiandrogen resistance
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Genomic amplification of the androgen receptor (AR) is an established mechanism of antiandrogen resistance in prostate cancer. Here we show that the magnitude of AR signaling output, independent of AR genomic alteration or expression level, also contributes to antiandrogen resistance, through upregulation of the coactivator GREB1. We demonstrate 100-fold heterogeneity in AR output within cell lines and show that cells with high AR output have reduced sensitivity to enzalutamide. Through transcriptomic and shRNA knockdown studies, together with analysis of clinical datasets, we identify GREB1 as a gene responsible for high AR output. We show that GREB1 is an AR target gene that amplifies AR output by enhancing AR DNA binding and promoting p300 recruitment. GREB1 knockdown in high AR output cells restores enzalutamide sensitivity in vivo. Thus, GREB1 is a candidate driver of enzalutamide resistance through a novel feed forward mechanism.
Overall design AR ChIP was performed on LNCaP prostate cancer cells with high AR activity infected with shRNA against Renilla or GREB1
Contributor(s) Lee E, Sawyers CL, Wang P, Zheng D
Citation(s) 30644358
Submission date Oct 01, 2018
Last update date Mar 27, 2019
Contact name Deyou Zheng
Organization name Albert Einstein College of Medicine
Street address 1301 Morris Park Ave
City Bronx
State/province NY
ZIP/Postal code 10461
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM3408176 AR_high_shRenilla_ChIP
GSM3408177 AR_high_shRenilla_input
GSM3408178 AR_high_shGREB1_ChIP
BioProject PRJNA494088
SRA SRP163001

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
GSE120680_RAW.tar 986.7 Mb (http)(custom) TAR (of TDF)
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