Preclinical Evaluation of Serine/Threonine Kinase Inhibitors Against Prostate Cancer Metastases

Abstract

A central tenet of the field of bone metastases is that the bone microenvironment supplies factors, such as TGF-beta, stimulating prostate cancer cell signaling and altering their phenotype. TGF-beta signaling in cancer is however complex and can lead to the activation of numerous genes. We have identified many of these genes by microarray analysis and have validated the gene reported here. Of these, PMEPA1 as the most highly upregulated gene. We have cloned the PMEPA1 promoter and full-length gene and have begun promoter analysis of the TGF-beta response element. We are in the process of overexpressing PMEPA1 in prostate cancer lines. In vivo experiments are in progress to determine the effect of a TGF-beta RI kinase inhibitor, SD-208, on the development and progression of prostate cancer metastases to bone due to PC-3, LuCAP and C42B prostate cancers.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2005
Accession Number
ADA462851

Entities

People

  • Theresa Guise

Organizations

  • University of Virginia

Tags

DTIC Thesaurus Topics

  • Bone And Bones
  • Bone Diseases
  • Cancer
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Genetics
  • Growth Factors
  • Inhibitors
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Polymerase Chain Reaction
  • Prostate
  • Prostate Cancer
  • Proteins
  • Tissues

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.
  • Prostate Cancer Biology.