The Role of Stromally Produced Cathepsin D in Promoting Prostate Tumorigenesis

Abstract

Stromal-epithelial interactions are important in development and cancer of the prostate. Estrogen receptor functions as a transcription factor to regulate gene expression. One such ERregulated gene is the protease cathepsin D (CathD). This proposal has two immediate objectives. The first is to determine how overexpression of cyclin D1 (CD1) in the stroma induces the upregulation of the estrogen regulated gene CathD. The second objective is to determine how overexpression of CathD in the stroma can contribute to tumorigenesis in the epithelium. Results show 1) CD1 interacts with the ER-alpha to modify the expression of estrogen regulated genes like CathD in prostate fibroblasts. 2) ER signaling in the stroma contributing to CAFs induced tumorigenesis in adjacent epithelium. 3) Stromal specific overexpression of CathD promotes prostate tumorigenesis through activation of TGF--beta signaling pathways.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2014
Accession Number
ADA621186

Entities

People

  • Freddie Pruitt

Organizations

  • Vanderbilt University

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Epithelial Cells
  • Estrogens
  • Fibroblasts
  • Gene Expression
  • Hormones
  • Molecules
  • Prostate
  • Prostate Cancer
  • Proteins
  • Sex Hormones
  • Tissues

Readers

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  • Molecular and genetic basis of cancer.