The primary objectives of this proposal are to purify prostatic growth factor (PrGF) to homogeneity and further define its physiochemical and biological characteristics. Work in our laboratory has established that a growth factor is present in normal postpubertal prostate, BPH, and carcinoma of the prostate that is a mitogen for fetal rat osteoblasts and fibroblasts, human foreskin fibroblasts (HFF), and human prostate-derived fibroblasts in tissue culture. An isolation scheme has been used to obtain PrGF from BPH tissue. The activity of PrGF has been increased 1400-fold. As little as 4 ng/ml of the purified factor was equivalent to 10% serum in promoting HFF proliferation. PrGF has an apparent molecular weight of about 1700 daltons, an isoelectric point of 4.3 to 5.4, and is both heat and acid labile. PrGF does not compete for EGF receptor binding. The properties of PrGF differ from other known growth factors. Initial studies on the biologic characterization of PrGF have shown that tissue extracts from BPH stimulate fibroblasts derived from the same prostate to undergo mitoses in tissue culture. This apparent paracrine activity of PrGF may be important in the development of fibrostromal nodules in human BPH. In this proposal we have outlined experiments to prepare a monoclonal antibody to PrGF and, in turn, use this antibody to provide mg quantities of highly purified growth factor using affinity chromatography. We further propose to use this antigen and antibody to develop a RRA and a RIA to PrGF. The antibody will also be used to localize PrGF in prostatic tissue. Studies are also proposed to determine the interaction, if any, between PrGF and steroid hormones in target tissues. Additional studies are proposed to determine if the synthesis and/or secretion of PrGF is controlled by hormones. Finally, we propose to initiate a long-range study to determine the concentration of PrGF in prostates of various size and age. These studies are directed at determining the role of PrGF in the etiology of human BPH.
