Identification of Sonic Hedgehog-Induced Stromal Factors That Stimulate Prostate Tumor Growth

Abstract

We will determine the mechanism by which Shh signaling accelerates prostate tumor growth, identify Shh targets in prostate tumor stroma, and test the effect of individual target genes on tumor growth. The purpose of the report is to evaluate the second year of research. We reduced autocrine signaling in LNShh cells and found that this does not disrupt increased growth of LNShh tumors. This shows that autocrine Shh signaling is not involved in tumor growth. We evaluated Shh signaling in human prostate tumors. In our mouse model system, we have identified 9 stromal genes that may be involved in tumor growth that is stimulated by Shh Only one gene is over-expressed in prostate cancer compared to normal prostate. Since Shh signaling is present in tumor stromal cells, we evaluated the role of different stromal phenotype in Shh signaling. Human benign and cancer samples were stained for myofibroblasts. We found that increased numbers of myofibroblasts relates to expression of each of the nine genes we identified in the xenograft model. Tumors with reactive stroma also have increased proliferation. These data may assist in predicting prostate tumor recurrence.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2007
Accession Number
ADA485392

Entities

People

  • Aubie Shaw
  • Wade Bushman

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Biology
  • Cells
  • Culture Techniques
  • Developmental Biology
  • Embryos
  • Growth Factors
  • Medical Personnel
  • Molecular Biology
  • Muscle Cells
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Prostate Cancer
  • Stem Cells
  • Stromal Cells
  • Tissues

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Biology and Genetics
  • Oncology (Cancer Research).