Analysis of the Role of the Wnt/B-Catenin Pathway in Prostate Development and Tumorigenesis

摘要

We have continued studies which are focused on understanding how dysregulation of the Wnt/B-catenin signaling pathway are causally associated with prostate tumorigenesis. We have created a mouse model in which B-catenin signaling is activated and found that these mice develop prostate tumors with 100% penetrance. This process initiates with small areas of prostatic hyperplasia as early as 4.5 weeks of age, continues on to lesions resembling prostatic intraepithelial neoplasia (PIN), and progresses to invasive prostate carcinoma by % months of age. We are currently examining these mice at older ages to determine if the tumors metastasize. In addition, we have found that these tumors are initially androgen sensitive, based on the apoptotic response of these tumors to surgical castration. Finally, we are embarking on studies to determine if activation of B-catenin signaling can synergize with other genetic lesions in prostate cancer progression.