Role of Stromally Produced Cathepsin D in Promoting Prostate Tumorigenesis.

摘要

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.