Transforming growth factor beta-1 and beta-2 and type II receptor functional regulation of ALVA-101 human prostate cancer cells

Transforming growth factor beta-1 (IGF beta-1) causes apoptosis of many epithelial cells, including the prostate, but other secondary effects of TGF beta-1 may be important in carcinogenesis. In a human prostate cancer cell line (ALVA-101), we determined the effects of TGF beta-1 and TGF beta type I and II receptor antibody on cell proliferation and TGF beta-1 receptor binding. TGF beta-1 and -2 and TGF beta type II receptor mRNA expression levels were determined by polymerase chain reaction (PCR) and Northern blot analysis. A dose-responsive suppression (0.03 to 10 ng/mL) was observed for cells treated with TGF beta-1 from 3 to 7 days (P < .01). Untreated cells had 1.1 x 10(3) (n = 3) TGF beta receptors per cell, with a K-d of 0.20 nmol/L (n = 3) as determined by Scatchard analysis; treatment for 3 days with TGF beta-1 (1 ng/mL) reduced the receptor number (0.9 x 10(3)) and the K-d (0.12 nmol/L). Antibodies to TGF beta type I and II receptor stimulated proliferation with or without added TGF beta-1 (50% +/- 5% above control, P < .01, n = 6). TGF beta-1 and -2 and TGF beta type II receptor mRNA expression was observed in untreated cells. In cells treated with TGF beta-1, TGF beta-1 mRNA was not affected by treatment, but expression levels of the TGF beta type II receptor and TGF beta-2 mRNA were moderately suppressed after 72 hours of treatment. Control cells actively produced TGF beta-1 as measured by radioimmunoassay. The active and inactive forms of TGF beta-1 were approximately equal, but TGF beta-2 was secreted in smaller quantities than TGF beta-1 and the inactive form of TGF beta-2 predominated, with very small amounts of the active form. Our results suggest that the human prostate cancer cell line ALVA-101 retains negative control of proliferation in response to TGF beta-1. Inhibition of endogenous TGF beta action by antibodies to its receptor enhances the growth of ALVA-101 human prostate cancer cells, suggesting that endogenous TGF beta exerts an inhibitory control on their growth and cellular function. Copyright (C) 1999 by W.B. Saunders Company.