TGF-BETA-3 EXPRESSION CORRELATES WITH EPITHELIAL-CELL DEATH IN NORMAL, HYPERPLASTIC AND MALIGNANT PROSTATE

Cytokines of the TGF beta family are thought to be involved in cellula r growth control and are therefore likely candidates to regulate homeo stasis of the prostate. We have analyzed immunohistochemically the exp ression of TGF-beta 3 in normal prostate (NP), benign prostate hyperpl asia (BPH) and prostate cancer (PCa). Its expression was correlated to cell death and cell proliferation using double labeling techniques wi th terminal transferase and anti-Ki67 antibodies, respectively. TGF-be ta 3 expression, localized to the basal cell layer of glandular epithe lium, was found in NP and BPH. In TGF-beta 3 positive regions cell dea th was frequently detected, while proliferating cells were only observ ed in TGF-beta 3 negative areas. Moreover, cell death was not observed in the absence of TGF-beta 3. PCa was characterized by high cell prol iferation and the absence of cell death. TGF-beta 3 expression could n ot be detected in PCa. Hormonal ablation is the main therapeutic proto col used today suffering, however, from a high relapse rate. We have u sed the rat as a model system to show that castration, resulting in ma ssive cell death of glandular epithelial cells, induces overall expres sion of TGF-beta 3 in the basal cell layers. Interestingly, investigat ion of tumor material from patients received after hormonal ablation r evealed the simultaneous presence of TGF-beta 3 positive, hyperplastic regions undergoing cell death and TGF-beta 3 negative highly prolifer ating malignant foci. Our results suggest that the expression of TGF-b eta 3 strictly correlates with cell death in normal and hyperplastic p rostate and that disappearance of TGF-beta 3 indicates high cell proli feration and the establishment of the malignant phenotype.