The role of SKP2 in docetaxel response and resistance in prostate cancer.

e15058 Background: Docetaxel, a microtubule-targeting agent, is the current standard of care for symptomatic metastatic castrate-resistant prostate cancer. Understanding the mechanisms underlying docetaxel resistance may help clinicians tailor patient treatment and develop strategies to overcome resistance. Our analysis identified the underexpression of S-phase kinase associated protein 2 (SKP2) as a potential novel docetaxel resistance marker. SKP2 ubiquitinates and degrades p27Kip1, a tumor suppressor which inhibits kinases that control progression to the S-phase of the cell cycle. Elevated SKP2 degrades p27Kip1, which in turn leads to uncontrolled proliferation. In this study, we investigated the effect of modulating SKP2 expression on docetaxel-response in a human prostate cancer cell line, DU145. Methods: Publicly available datasets were analyzed to identify transcripts whose expression correlated with docetaxel-resistance. The impact on docetaxel-response from changing the expression levels of one o...