MESENCHYMAL EPITHELIAL INTERACTIONS AND TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION DURING NORMAL AND ABNORMAL PROSTATIC GROWTH

Mesenchymal-epithelial interactions are associated with growth and mor phogenesis of the prostate. We have detected three isoforms of transfo rming growth factor beta (TGF-beta) in the developing mouse prostate t hat may mediate some of these interactions. Separation of the fetal ur ogenital sinus (UGS) tissue into mesenchymal and epithelial components indicated that mRNA expression of TGF-beta 1, 2, and 3 was more abund ant in the mesenchyme compared to the epithelium. Immunohistochemical analysis revealed accumulation of TGF-beta 1 in the mesenchyme surroun ding ductules in the UGS and neonatal prostate. Further analysis of TG F-beta 1 localization in surgically removed adult human prostate tissu es revealed more intense staining associated with regions of abnormal growth compared to normally appearing tissue. The percent of the total stained area with extracellular accumulation of TGF-beta 1 was 59% in prostate cancer, 26% in benign prostatic hyperplasia (BPH), and 8.6% in normal tissue. In additional immunohistochemical studies we observe d that intracellular TGF-beta 1 was predominantly associated with the epithelial cells in prostate cancer (epithelial cells = 33.5% of the t otal stained area, stromal cells = 13.3%, and unstained = 53.2%), wher eas in BPH intracellular TGF-beta 1 was predominantly associated with stromal cells (stromal cells = 32.2% of the total stained area, epithe lial cells = 12.3%, and unstained = 55.5%). Although additional experi mental and clinical studies are needed to better understand the relati onships between TGF-beta 1 and abnormal prostatic growth, our observat ions thus far suggest a role for TGF-beta 1 in the development of beni gn and malignant growth abnormalities in the prostate. One approach to establishing the pathobiological significance of TGF-beta 1 acccumula tion in the prostate is by introducing and overexpressing the TGF-beta 1 cDNA in prostate tissue using the mouse prostate reconstitution mod el system. We discuss applicability of transgenic animal and organ rec onstitution models for experimental studies concerning TGF-beta-induce d prostate growth abnormalities. (C) 1995 Wiley-Liss, Inc.