Utilizing a series of novel murine recombinant retroviruses which contain the human androgen receptor (hAR) gene, the v-gagmyc oncogene, TGF-b genes, and the b-FGF gene together with the bacterial beta-galactosidase gene (for visualization in tissue sections), the effects of overexpressing these genes on the growth and differentiation of the mouse prostate will be studied. The investigators will test the stromal-epithelial interaction hypothesis by introducing these genes specifically into mesenchymal cells and combining them with either normal, genetically unaltered, or myc-infected epithelium. By this approach both the gene specificity and gene complementarity with respect to stromal-epithelial interactions will be addressed. They will further probe the mechanism(s) of BPH by a combined immunohistochemical/molecular approach that will differentiate exogenous and endogenous growth factor expression and demonstrate possible field effects resulting from positive autoregulation of growth factor expression, shown previously to occur in the case of TGF-b. These studies, as well as northern and southern blotting analysis, will further test the hypothesis that BPH nodules result from growth factor recruitment of adjacent normal cells and/or clonal expansion by altered cells with enhanced growth potential.
