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Series GSE80256 Query DataSets for GSE80256
Status Public on Apr 01, 2017
Title Grainyhead-like 2 is essential for androgen receptor expression and activity in prostate cancer (ChIP-seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The mainstay treatment for men with metastatic prostate cancer is androgen deprivation therapy (ADT), which inhibits androgen biosynthesis and/or binding of ligand to the androgen receptor (AR). Most men respond to ADT, but all subsequently develop resistance and progression to incurable and lethal castration-resistant prostate cancer (CRPC). CRPC generally remains driven by the AR: therefore, the development of novel AR-targeted therapies, as well as elucidating therapy-driven changes to the AR signalling axis that mediate resistance, remain priorities for the field. Using a novel and powerful proteomic technique, rapid immunoprecipitation of endogenous proteins (RIME), we have identified a new AR binding protein, the transcription factor Grainyhead-like 2 (GRHL2), and shown that it plays an essential, multifaceted role in signalling by the canonical AR and by constitutively active truncated AR variants (ARVs). GRHL2 is necessary for the maintenance of AR/ARV expression in multiple prostate cancer model systems, co-localises with AR at specific sites on chromatin to enhance the androgen-regulated transcriptional program, and is required for optimal prostate cancer growth. Interestingly, we found that GRHL2 is itself an AR/ARV-regulated gene, creating a positive feed-forward loop between the two factors. The GRHL2 gene is frequently amplified and upregulated in CRPC, thereby potentially enabling further amplification AR signalling in the drug-resistant setting. In summary, this study has identified a critical new AR coregulator and potential therapeutic target in prostate cancer.
 
Overall design ChIP-seq for GRHL2 and AR in LNCaP cells
 
Contributor(s) Selth L
Citation(s) 28473532
Submission date Apr 13, 2016
Last update date May 15, 2019
Contact name Luke Selth
E-mail(s) luke.selth@adelaide.edu.au
Organization name University of Adelaide
Department School of Medicine
Lab Dame Roma Mitchell Cancer Research Laboratories
Street address Frome Rd
City Adelaide
State/province SA
ZIP/Postal code 5000
Country Australia
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (4)
GSM2122802 GRHL2_ChIP-seq_replicate1
GSM2122803 GRHL2_ChIP-seq_replicate2
GSM2122804 AR_ChIP-seq_replicate1
This SubSeries is part of SuperSeries:
GSE80452 Grainyhead-like 2 is essential for androgen receptor expression and activity in prostate cancer
Relations
BioProject PRJNA318399
SRA SRP073261

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
GSE80256_RAW.tar 1.9 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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