title: Transforming growth factor beta-1 and beta-2 and type II receptor functional regulation of ALVA-101 human prostate cancer cells.
abstract: Transforming growth factor beta-1 (TGFbeta-1) causes apoptosis of many epithelial cells, including the prostate, but other secondary effects of TGFbeta-1 may be important in carcinogenesis. In a human prostate cancer cell line (ALVA-101), we determined the effects of TGFbeta-1 and TGFbeta type I and II receptor antibody on cell proliferation and TGFbeta-1 receptor binding. TGFbeta-1 and -2 and TGFbeta 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 TGFbeta-1 from 3 to 7 days (P < .01). Untreated cells had 1.1 x 10(3) (n = 3) TGFbeta receptors per cell, with a Kd of 0.20 nmol/L (n = 3) as determined by Scatchard analysis; treatment for 3 days with TGFbeta-1 (1 ng/mL) reduced the receptor number (0.9 x 10(3)) and the Kd (0.12 nmol/L). Antibodies to TGFbeta type I and II receptor stimulated proliferation with or without added TGFbeta-1 (50% +/- 5% above control, P < .01, n = 6). TGFbeta-1 and -2 and TGFbeta type II receptor mRNA expression was observed in untreated cells. In cells treated with TGFbeta-1, TGFbeta-1 mRNA was not affected by treatment, but expression levels of the TGFbeta type II receptor and TGFbeta-2 mRNA were moderately suppressed after 72 hours of treatment. Control cells actively produced TGFbeta-1 as measured by radioimmunoassay. The active and inactive forms of TGFbeta-1 were approximately equal, but TGFbeta-2 was secreted in smaller quantities than TGFbeta-1 and the inactive form of TGFbeta-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 TGFbeta-1. Inhibition of endogenous TGFbeta action by antibodies to its receptor enhances the growth of ALVA-101 human prostate cancer cells, suggesting that endogenous TGFbeta exerts an inhibitory control on their growth and cellular function.
authors.affiliation: Department of Medicine and Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Meikle
authors.forename: R E
authors.initials: RE
authors.lastname: Swope
authors.forename: D Y
authors.initials: DY
authors.lastname: Yin
authors.forename: D
authors.initials: D
authors.lastname: Fullmer
authors.forename: S M
authors.initials: SM
authors.lastname: Loop
authors.forename: D K
authors.initials: DK
authors.lastname: Murray
mesh_terms: D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta