Accession Number:

ADA446897

Title:

Identify the impact of TGF-B Signaling on the Stroma in the Progression of Prostate Cancer

Descriptive Note:

Annual rept. 1 Mar 2004-28 Feb 2005

Corporate Author:

VANDERBILT UNIV NASHVILLE TN

Personal Author(s):

Report Date:

2005-03-01

Pagination or Media Count:

10.0

Abstract:

As a result of androgen ablation TGF-Beta expression levels transiently elevate and regression of benign prostate hyperplasia as well as prostate cancer cells for the most part occur. Better understanding of prostate- androgen responsiveness is critical in understanding and ultimately combating androgen-non-responsive prostate cancer. Studying the conditional TGF-Beta type II receptor fibroblast knockout mouse model we developed Tgfbr2fspko, we found that TGF-Beta signaling in the prostate stromal fibroblasts regulate both stromal and epithelial differentiation in the prostate. Notably the data dispels previous reports that TGF-Beta signaling is required for myofibroblast differentiation. As proposed we attempted to develop mice that are stromally knocked out for TGF-Beta signaling and express the large T antigen in the prostate epithelia, but was unsuccessful. We have however acquired techniques in our laboratory to perform tissue recombination experiments where the identical cell types prostate stroma and epithelia can generate prostate glands through xenografting, that display similar phenotypic characteristics of intact mice. We hope to gain permission to progress with these experiments in order to address the mechanism of stromal TGF-Beta signaling impact on prostate cancer androgen responsiveness.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE