We have described a prostatic cell derived growth factor (PRGF) from a human prostatic epithelial cancer cell line JCA-1. PRGF is a protein, constitutively produced by JCA-1 cells and released into the culture medium. PRGF was purified and shown to have a molecular weight of 53,100. A partial amino acid sequence from the N-terminal of PRGF has been obtained. The interaction between stromal fibroblast preparations, from human prostate or nonprostate fibroblasts, and PRGF causes an accelerated growth of the fibroblasts. The mechanism includes an increase in growth rate and a more rapid entry of G1 phase cells into the replicating S-phase of the cell cycle. PRGF may represent a paracrine growth factor and is distinct from the commonly known growth factors. Since prostate growth involves both epithelium and fibromuscular tissue, and prostate hyperplasia and malignancy are sometimes characterized by abnormal fibroblast- epithelial cell interactions, we plan to investigate the nature and biological activity of the PRGF. We will further characterize and identify PRGF from JCA-1 cancer cell culture supernatant. PRGF needs to be characterized to further identify its amino acid sequence and production of polyclonal and monoclonal antibodies to investigate its biological functions. Sensitive assay procedures, such as cell cycle analysis, cell size, DNA replication, etc. will be developed to identify PRGF. The biological activity of PRGF will be pursued by identifying the cell types in the prostate, whether stromal or epithelial, responding to PRGF. Growth responses of different cell types will be measured and cell surface receptors, specific for PRGF, will be identified using radiolabeled PRGF. Localization of the PRGF production site in clinical prostate tissues will be pursued using the peroxidase antibody technique. Normal, benign and cancer tissues from the prostate will be analyzed in order to correlate PRGF and prostate cancer gradings. Furthermore, the relationship between PRGF production and androgen stimulation will be analyzed using JCA-1 cells. Further structural analysis of PRGF, using isolated JCA-1 cDNA and PRGF nucleotide sequence is planned. The cDNA clone will also make it possible to heterologously express the PRGF protein.
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