|
| Status |
Public on Feb 16, 2018 |
| Title |
Bypassing drug-resistance mechanisms of prostate cancer with small-molecules that target androgen receptor chromatin interactions |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Human androgen receptor (AR) is a hormone-activated transcription factor that is an important drug-target in the treatment of prostate cancer. Current small molecule AR-antagonists (such as Enzalutamide) compete with male hormones that bind to the steroid binding pocket of the AR ligand binding domain (LBD). In castration-resistant prostate cancer (CRPC), drug-resistance can manifest through AR-LBD mutations that convert AR-antagonists into agonists, or by expression of AR-variants lacking the LBD. Such treatment resistance underscores the importance of novel ways of targeting the AR. In this study, we tested whether VPC14449, a small molecule inhibitor that was rationally designed to selectively target the AR DNA binding domain (DBD), could directly interfere with AR-DNA interactions. Using ChIP-seq in cell line models expressing AR or AR variants, we found that genome-wide chromatin binding of AR was dramatically impacted by VPC14449 (although with lesser effect on AR variants).
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| |
|
| Overall design |
AR and AR variant ChIP-seq in R1-AD1 and R1-D567 prostate cancer cells with VPC14449 treatment
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| |
|
| Contributor(s) |
Yang R, Che M, Dehm SM |
| Citation(s) |
28775145 |
| |
| Submission date |
Mar 10, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Scott M Dehm |
| E-mail(s) |
dehm@umn.edu
|
| Organization name |
University of Minnesota
|
| Department |
Masonic Cancer center
|
| Lab |
Dr Dehm M. Scott
|
| Street address |
8806 420 Delaware
|
| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55414 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (7)
|
|
| Relations |
| BioProject |
PRJNA378776 |
| SRA |
SRP101727 |
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