Prostatic Growrh Factors (PrGFs)——From the Identification of Probasin to the Role of PrGFs

Abstract

Rat prostates contain a unique androgen-regulated protein of 19-21 kilodaltons, “probasin” (prostatic basic protein), that is statistically related to members of alpha-2-microglubulin ligand carrier family. Probasin has low but distinct growth factor activity as determined by DNA synthesis stimulation with BALB/c 3T3 fibroblasts. With this as turning point, we have studied identification and significance of prostatic growth factors. Rat dorsolateral prostate contains heparin-binding growth factors(HBGFs or FGFs) and prostatic EGF-related mitogen (PEM); PEM is a member of the non-HBGF family that is the major growth factor in normal prostate but hardly detectable in prostate tumor tissues. In human pathologic prostates, HBGFs are major growth factors both in benign prostatic hypertrophy (BPH) tissues and in prostate cancer. The HBGF content in BPH tissues is higher than in prostate cancer, whereas osteoblast growth factor (OGF) as assayed by DNA synthesis stimulation using MC3T3-E1 osteoblasts is higher in prostate cancer. A metastatic cell line, AT-3, established from the Dunning rat prostatic carcinoma produces OGF, insulin-like growth factor II (IGF-II) and transforming growth factor beta (TGF-,B). PEM and OGF, both of which have low affinity for heparin, are different from each other in stability to heat and acid treatments. Partially purified OGF contains IGF-II and TGF-s in addtion to an acid labile polypeptide growth factor with a molecular weight of about 19 kilodaltons. Cell lines with high potency for metastasis (AT-3, MAT-LyLu and MAT-Lu), established from the Dunning rat prostatic carcinoma, can produce higher amount of IGF-II. TGF-s at a concentration as low as 0.05 ngjml either stimulatesd attachment or detachment of AT-3 cells, depending on the kind of culture media. Detached AT-3 cells are able to grow in suspension. TGF-s stimulates cell growth of MC3T3-E1 osteoblasts.