Transcriptional regulation of initiation and progression of prostate cancer
Prostate cancer (PCa) continues to be the most common malignancy diagnosed in American men and the second leading cause of male cancer mortality. Major efforts have been directed to identify early detection and prognostic markers of the disease. In contrast, significantly less research has been devoted to understand the molecular mechanisms of PCa pathogenesis. Published studies from our laboratory demonstrated that elevated levels of Foxm1 protein are associated with high proliferation rates in human prostate adenocarcinomas and are directly correlated with the grade of human PCa. To study the exact signaling pathways involved in pathogenesis of PCa we are using TRAMP, PTEN-/- and orthotopic mouse models.
The focus of this project is to identify the direct role of several transcription factors (Foxm1, Foxf1, Foxf2, SPDEF) in prostate epithelial cells and cells of tumor microenvironment during initiation and progression of PCa and its potential regulation by p19ARF tumor suppressor.