Dose-dependent effects of small-molecule antagonists on the genomic landscape of androgen receptor binding.

ABSTRACT:

Background

The androgen receptor plays a critical role throughout the progression of prostate cancer and is an important drug target for this disease. While chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) is becoming an essential tool for studying transcription and chromatin modification factors, it has rarely been employed in the context of drug discovery.

Results

Here we report changes in the genome-wide AR binding landscape due to dose-dependent inhibition by drug-like small molecules using ChIP-Seq. Integration of sequence analysis, transcriptome profiling, cell viability assays and xenograft tumor growth inhibition studies enabled us to establish a direct cistrome-activity relationship for two novel potent AR antagonists. By selective

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC3507642 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature