Beta-Catenin and Prostate Development

描述（由申请人提供）：

DESCRIPTION (provided by applicant): My goal as an independent researcher is to use a two-pronged approach to study prostate disease: (1) I will use the developing prostate as a model system for elucidating previously unrecognized signaling pathways that contribute to prostate growth and (2) I will investigate these signaling pathways in clinically relevant models of benign prostate hyperplasia or prostate cancer. My research focus in this proposal is to test the overarching hypothesis that beta-catenin is required for prostate ductal development in the embryonic mouse prostate anlagen, the urogenital sinus (UGS). The first two specific aims will investigate the function of beta-catenin during prostatic budding. They will test hypotheses that (1) androgens stimulate beta-catenin-mediated transcription in the UGS and that beta-catenin is required for budding, and (2) beta-catenin mediates cell adhesion during prostatic bud formation and that this action of beta-catenin is required for budding. The last aim investigates the regulation of beta-catenin during budding. It will test the hypothesis that (3) fibroblast growth factor 10 is required for stabilizing beta-catenin during prostatic budding. This research plan has a high probability of leading to the identification of beta-catenin as a central player in prostatic budding. My plan is to use the above results as preliminary data to apply, in year 3 of this award, for an RO1 or R03 grant focused on mechanisms of benign prostate hyperplasia or prostate cancer. As a K01 recipient, I will follow a career development plan with very specific research and development milestones for each award year. I will meet regularly with my mentors and advisory committee and complete didactic coursework in cancer biology. I will obtain experiential training in grant writing, Wnt/ beta-catenin signaling, benign prostate hyperplasia, and prostate cancer. This plan will stretch my research expertise and enhance my training in prostate disease research. The University of Wisconsin is an NIDDK-sponsored O'Brien Urology Research Center, an NCI-sponsored Comprehensive Cancer Center, and boasts nearly 40 prostate research labs, culminating in an ideal training environment for me as a future prostate scientist. Biological factors regulating growth during prostate development are also believed to be responsible for inappropriate growth during prostate disease. The proposed research will investigate how the beta-catenin protein interacts with male sex hormones to control prostate development, as these interactions might provide clues for how inappropriate prostate growth is activated during prostate disease.