Novel Effectors of TGF-Beta Signaling in Prostate Growth Regulation and Tumor Progression

Transforming growth factor-B (TGF-B) is a negative regulator of normal, benign and malignant prostate growth. Whiel serving a growth-inhibitory/apoptic role in the normal prostate, overproduction of TGF-B1 in the aging prostate contributes to the development of benign prostate hyperplasis (BPH) and prostate cancer. In this propoal, we hypothesize that TGF-B1 signaling via changes in Smad4-independent intracellular effectors and cross-talk with the adrogen receptor (AR) regulates prostate growth, and functional inactivaion of this network accelerates the manifestation of the malignant phenotype and tumor progression.