This proposed study will focus on the investigation of cellular mechanisms of stromal-epithelial interaction in the rat prostate gland as an extension of our previously funded program which stressed on the study of tissue interactions in vivo. In this study, we will pursue two major objectives: 1. We will define the role of dihydrotestosterone (DHT) in stromal-epithelial interactions in the rat prostate gland. This goal will be accomplished first by establishing viable cell lines that represent rat prostatic epithelial, fibroblast, and smooth muscle cells. We will clone a DHT-responsive fibroblast cell line which will allow us to assess the role of fibroblast in regulating androgen-induced DNA synthesis and gene expression by the prostatic epithelium. The possible mechanism of """"""""indirect"""""""" action of DHT on growth and differentiation of prostatic epithelium mediated by prostatic fibroblast, in the form of growth factor(s). extracellular matrix and intracellular signals, will be examined. 2. We will take advantage of certain established specificities of fetal adult tissue interactions in the rat prostate gland to isolate a fetal urogenital sinus-derived growth factor(s) (UGSGF). We will employ an established prostatic cell culture system for the detection of UGSGF. The possibility that this growth factor may be closely related to the family of basic fibroblast growth factor will be investigated. In order to obtain this material in sufficient quantity and to purify it for other relevant biological studies (e.g., specificity, dose response relationship, interaction with DHT and other growth factors, UGSGF receptor(s) and in vivo growth and regenerative activity), we propose to use molecular biology techniques and to prepare monoclonal antibodies to facilitate our progress in achieving these goals.
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