The development of many tissues during organogenesis is a result of interactions between stroma and epithelium. The stroma specifies and directs the morphogenesis and cytodifferentiation of the epithelium. Such interactions occur in the development of the prostate gland (urogenital sinus) and are androgen-regulated. Little is known about the molecular basis of these tissue interactions. Benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma are diseases of the prostate gland with unknown etiology. Since these disorders are characterized by abnormal proliferation and cytodifferentiation of cells, the concept of altered stromal-epithelial interaction in prostatic pathogenesis has gained considerable attention. Previous studies in my laboratory have identified a humoral factor (UGS factor) produced by urogenital sinus (UGS) which affects epithelial cell proliferation and phenotype. The UGS factor shares several properties with transforming growth factor-beta (TGF-beta). The overall goal of this proposal is to determine the role of UGS factor in affecting phenotype of epithelial cells and assessing its significance in stromal-epithelial interactions. An in vitro model is proposed based on our previous studies. Studies are designed to: 1. Determine in defined medium the steroid regulation and optimization of UGS factor synthesis and secretion from UGS organ explants and fibroblast monolayer cultures; 2. Determine the physico-chemical properties of UGS factor, develop a purification protocol, and assess its similarity to TGF-beta and; 3. Assess the regulation of epithelial phenotype by UGS factor using Northern analysis of prostate-specific gene expression (C1, C2, and C3 peptides of prostatein) and determining the membrane receptor through which UGS factor acts. These studies will identify the significance of UGS factor in stromal induction of epithelial phenotype in the prostate gland and lay the ground-work for determining the potential role of UGS factor in prostatic disease.
| Rowley, D R (1992) Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity. In Vitro Cell Dev Biol 28A:29-38 |
