Androgen Receptor Regulates a Distinct Transcription Program in Adrogen-Independent Prostate Cancer

INSTRUCTIONS: Please enter one of the following Topic Classifications in the section below: Bioinformatics & Computational Biology Genes & Environment Genetic & Molecular Epidemiology Medical Genomics Molecular Genetics Proteomics Statistical Genetics, Genomics, and Omics The evolution of prostate cancer from an androgen dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood.

We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation.