Accession Number:

ADA426168

Title:

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

Descriptive Note:

Annual rept. 1 Apr 2003-31 Mar 2004

Corporate Author:

VAN ANDEL RESEARCH INSTITUTE GRAND RAPIDS MI

Personal Author(s):

Report Date:

2004-04-01

Pagination or Media Count:

17.0

Abstract:

We have initiated studies to determine whether dysregulation of the WntBeta-catenin signaling pathway results in prostate disease. Our preliminary results show that prostate- specific deletion of Apc, a genetic alteration associated with increased levels of Beta- catenin, results in the induction of early onset prostate cancer. Analysis of older mice reveals these prostate tumors have the propensity to metastasize, at least to lymph nodes. To directly address whether Beta-catenin activation induces progression, we have created mice that allow us to induce expression of an oncogenic form of B-catenin in the prostate. We have also crossed the mice carrying the prostate specific deletion of Apc with mice deficient for the homeobox gene Nkx3.l. Nkx3.l-deficient mice reproducibly develop prostate hyperplasia and dysplasia, but show no signs of progression beyond this point. We are looking for synergistic effects of Wnt pathway activation and Nkx3.l loss in terms of time of tumor onset as well as metastatic spread.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE