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Series GSE89938 Query DataSets for GSE89938
Status Public on Aug 23, 2017
Title Targeting the androgen receptor N-terminus via the cochaperone Bag-1L [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Targeting the activation function-1 (AF-1) at the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the BAG domain of the cochaperone Bag-1L. Mutations in this domain or loss of Bag-1L abrogates AR signaling and reduces PCa growth. Correspondingly, Bag-1L protein levels increase with progression of primary prostate tumors to castration-resistant PCa, correlating inversely with patient response to abiraterone therapy. Intriguingly, BAG domain residues important for its interaction with the AR AF-1 overlap a potentially druggable pocket of this protein. Bag-1L is therefore a putative therapeutic target for the inhibition of AR AF-1 activity.
 
Overall design Androgen receptor (AR) ChIP-seq was carried out in LNCaP Talen Control, Bag-1L KO, Bag-1L KO plus Vector (control), Bag-1L KO plus (wild-type) Bag-1L, LNCaP plus wild-type Bag-1L and LNCaP plus CMut Bag-1L cells. Cells were cultured under hormone-starvation conditions for 72 h and then treated with vehicle (ETOH) or 10 nM DHT for 4 h prior to cell fixation and harvest. Experiments in LnCaP Talen Control and Bag-1L KO cells were carried out in duplicate.
 
Contributor(s) Cato L, Wu J, Cato AC, Brown M
Citation(s) 28826504
Submission date Nov 16, 2016
Last update date May 15, 2019
Contact name Laura Cato
E-mail(s) laura_cato@dfci.harvard.edu
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Street address 450 Brookline Ave., D728
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (24)
GSM2393828 LnCaP_Talen_Ctl_Veh_AR_Input_Reps1and2
GSM2393829 LnCaP_Talen_Ctl_Veh_AR_ChIP_Reps1and2
GSM2393830 LnCaP_Talen_Ctl_DHT_4h_Input_Reps1and2
This SubSeries is part of SuperSeries:
GSE89939 Targeting the androgen receptor N-terminus via the cochaperone Bag-1L
Relations
BioProject PRJNA354526
SRA SRP096060

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
GSE89938_RAW.tar 4.6 Gb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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