Mesenchymal-epithelial interactions and transforming growth factor-beta 1 expression during normal and abnormal prostatic growth.

Mesenchymal-epithelial interactions are associated with growth and morphogenesis of the prostate. We have detected three isoforms of transforming growth factor beta (TGF-beta) in the developing mouse prostate that may mediate some of these interactions. Separation of the fetal urogenital sinus (UGS) tissue into mesenchymal and epithelial components indicated that mRNA expression of TGF-beta 1, 2, and 3 was more abundant in the mesenchyme compared to the epithelium. Immunohistochemical analysis revealed accumulation of TGF-beta 1 in the mesenchyme surrounding ductules in the UGS and neonatal prostate. Further analysis of TGF-beta 1 localization in surgically removed adult human prostate tissues 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 observed that intracellular TGF-beta 1 was predominantly associated with the epithelial cells in prostate cancer (epithelial cells = 33.5% of the total stained area, stromal cells = 13.3%, and unstained = 53.2%), whereas in BPH intracellular TGF-beta 1 was predominantly associated with stromal cells (stromal cells = 32.2% of the total stained area, epithelial cells = 12.3%, and unstained = 55.5%). Although additional experimental and clinical studies are needed to better understand the relationships between TGF-beta 1 and abnormal prostatic growth, our observations thus far suggest a role for TGF-beta 1 in the development of benign and malignant growth abnormalities in the prostate. One approach to establishing the pathobiological significance of TGF-beta 1 accumulation in the prostate is by introducing and overexpressing the TGF-beta 1 cDNA in prostate tissue using the mouse prostate reconstitution model system. We discuss applicability of transgenic animal and organ reconstitution models for experimental studies concerning TGF-beta-induced prostate growth abnormalities.