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

• Published in: Metabolism, clinical and experimental clinical and experimental, 1999-09, Vol.48 (9), p.1075-1081
• Main Authors: Meikle, A.Wayne, Swope, Richard E., Yin, Diana Y., Fullmer, Dan, Loop, Steven M., Murray, Darrell K.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Division - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Male; Medical sciences; Nephrology. Urinary tract diseases; Prostatic Neoplasms; Protein Binding - drug effects; Receptors, Transforming Growth Factor beta - metabolism; RNA, Messenger - metabolism; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(99)90118-X

Transforming growth factor beta-1 (TGFβ-1) causes apoptosis of many epithelial cells, including the prostate, but other secondary effects of TGFβ-1 may be important in carcinogenesis. In a human prostate cancer cell line (ALVA-101), we determined the effects of TGFβ-1 and TGFβ type I and II receptor antibody on cell proliferation and TGFβ-1 receptor bind ing. TGFβ-1 and -2 and TGFβ 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 TGFβ-1 from 3 to 7 days ( P < .01). Untreated cells had 1.1 × 10 3 (n = 3) TGFβ receptors per cell, with a K d of 0.20 nmol/L (n = 3) as determined by Scatchard analysis; treatment for 3 days with TGFβ-1 (1 ng/mL) reduced the receptor number (0.9 × 10 3) and the K d (0.12 nmol/L). Antibodies to TGFβ type I and II receptor stimulated proliferation with or without added TGFβ-1 (50% ± 5% above control, P < .01, n = 6). TGFβ-1 and -2 and TGFβ type II receptor mRNA expression was observed in untreated cells. In cells treated with TGFβ-1, TGFβ-1 mRNA was not affected by treatment, but expression levels of the TGFβ type II receptor and TGFβ-2 mRNA were moderately suppressed after 72 hours of treatment. Control cells actively produced TGFβ-1 as measured by radioimmunoassay. The active and inactive forms of TGFβ-1 were approximately equal, but TGFβ-2 was secreted in smaller quantities than TGFβ-1 and the inactive form of TGFβ-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 TGFβ-1. Inhibition of endogenous TGFβ action by antibodies to its receptor enhances the growth of ALVA-101 human prostate cancer cells, suggesting that endogenous TGFβ exerts an inhibitory control on their growth and cellular function.