Selective Gene Regulation by Androgen Receptor in Prostate Cancer
Annual summary 30 Sep 2011-29 Sep 2012
MICHIGAN UNIV ANN ARBOR
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Androgen binds to the androgen receptor AR and is required for prostate cancer initiation and progression. Although androgen ablation is initially an effective prostate cancer therapy, patients eventually develop resistance, but disease remains driven by AR. There is a need to identify AR gene programs that promote proliferation versus differentiation to design better treatments. Using mutant ARs as models of aberrant AR activity, I generated cell lines harboring wild-type and mutant ARs and analyzed proliferation, anchorage-independent cell growth and alterations in AR target genes. I also generated a multiplexed promoter assay for high-throughput screening HTS to identify compounds that selectively regulate AR. After assay optimization, the primary HTS was performed with 2,5000 compounds. A dose response assay identified several compounds that selectively regulate AR and will be further studied in cell-based assays.
- Anatomy and Physiology
- Medicine and Medical Research