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Series GSE49295 Query DataSets for GSE49295
Status Public on Jan 23, 2014
Title Inhibition of Androgen Receptor and β-catenin activity in prostate cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result in drug resistance and disease recurrence. Therefore, simultaneous targeting of multiple pathways could in principle be an effective new approach to treating prostate cancer. Here we provide proof-of-concept that a small molecule inhibitor of nuclear β-catenin activity (called C3) can inhibit both the AR and β-catenin signaling pathways that are often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer cell growth by disruption of both β-catenin/TCF and β-catenin/AR protein interaction, reflecting the fact that TCF and AR have overlapping binding sites on β-catenin. Given that AR interacts with, and is transcriptionally regulated by β-catenin, C3 treatment also resulted in decreased occupancy of β-catenin on the AR promoter and diminished AR and AR/β-catenin target gene expression. Interestingly, C3 treatment resulted in decreased AR binding to target genes accompanied by decreased recruitment of an AR and β-catenin cofactor, CARM1, providing new insight into the unrecognized function of β-catenin in prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft model, and blocked renewal of bicalutamide-resistant sphere forming cells, indicating the therapeutic potential of this approach.
Overall design Compare and contrast the expression profile of prostate cancer cells treated with a Wnt inhibitor (C3) with respect to β-catenin and AR knockdown (all samples in duplicates).
Contributor(s) Lee E, Madar A, David G, Garabedian MJ, DasGupta R, Logan SK
Citation(s) 24019458
Submission date Jul 28, 2013
Last update date May 15, 2019
Contact name Susan K. Logan
Organization name NYU School of Medicine
Department NYU Cancer Institute, Mol Pharm and Biochem
Street address 522 1st Ave, Smilow Research Building, Rm # 1211
City New York
State/province New York
ZIP/Postal code 10016
Country USA
Platforms (1)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
Samples (10)
GSM1196950 C3-1
GSM1196951 C3-2
GSM1196952 si-AR-1
BioProject PRJNA213558
SRA SRP028282

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Supplementary file Size Download File type/resource
GSE49295_isoform_exp_diff.xls.gz 46.0 Mb (ftp)(http) XLS
GSE49295_summary_isoforms_fpkm_tracking.xls.gz 4.3 Mb (ftp)(http) XLS
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