Role of TGF-beta in Prostate Cancer Progression
Abstract
There is strong evidence that inflammation and interactions with the surrounding stromal microenvironment are critical for cancer initiation and progression. As a major component of the stroma, fibroblasts are recognized as prominent modifiers of cancer progression. The contribution of carcinoma associated fibroblasts (CAF) to cancer has been approved and become accepted, research has been conducted to understand the mechanisms underlying this stromal-epithelial interaction. In this project we have demonstrated that relatively small changes in the expression levels of TGFbeta and SDF1/CXCL12 in human prostate cancer stromal cells can drive carcinogenesis in human prostatic epithelium. In two publications we showed linkage between the two pathways in that TGFbeta elevates CXCR4, the cognate receptor for SDF1, in the epithelial cells allowing activation of the SDF signaling pathway. This in turn activates Akt phosphorylation which is sufficient to suppress the growth inhibitory response to TGFbeta. This link provides a mechanism for the switch in TGFbeta activity from growth suppressive in normal tissue to growth promoting in cancer and suggests routes for therapeutic intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2008
- Accession Number
- ADA502784
Entities
People
- Mingfang Ao
Organizations
- Vanderbilt University Medical Center