Identify the Impact of TGF-Beta Signaling on the Stroma in the Progression of Prostate Cancer

Abstract

As a result of androgen ablation TGF- 1 expression levels transiently elevate and regression of benign prostate hyperplasia as well asprostate 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- type II receptor fibroblast knock out mouse model we developed (Tgfbr2fspko), we found that TGF- signaling in the prostate stromal fibroblasts regulate both stromal and epithelial differentiation in the prostate. Notably the data dispels previous reports that TGF- signaling is required for myofibroblast differentiation. As proposed we attempted to develop mice that are stromally knocked out for TGF- signaling and express the large Tantigen 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- signaling impact on prostate cancer androgen responsiveness.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2007
Accession Number
ADA475121

Entities

People

  • Neil A. Bhowmick

Organizations

  • Vanderbilt University

Tags

DTIC Thesaurus Topics

  • Ablation
  • Androgens
  • Apoptosis
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Epithelium
  • Fibroblasts
  • Growth Factors
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Prostate Cancer
  • Prostate Gland
  • Stromal Cells
  • Tissues

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Prostate Cancer Biology.