Analysis of the Role of the Wnt/Beta-Catenin Pathway in Prostate Development and Tumorigenesis
Final rept. 1 Apr 2003-31 Mar 2006
VAN ANDEL RESEARCH INSTITUTE GRAND RAPIDS MI
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We have continued studies which are focused on understanding how dysregulation of the WntB-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 7 months of age. We have examined these mice at older ages and found that these tumors do not appear to metastasize. In addition, we have found that these tumors are initially androgen sensitive, based on the apoptotic response of these tumors to surgical castration, however, mice examined five months after castration reveal small areas of hyperplasia occurring in an androgen-independent manner. Finally, we are embarking on studies to determine if activation of B-catenin signaling can synergize with other genetic lesions in prostate cancer progression.
- Medicine and Medical Research