TGF-beta inhibits the platelet-derived growth factor-induced formation of inositol trisphosphate in MG-63 human osteosarcoma cells.
Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and heparin-binding growth factor-1 (HBGF-1) stimulated the proliferation of a variant of the human osteosarcoma cell line, MG-63-LS (LS = low serum). Transforming growth factor beta (TGF-beta) completely inhibited cell growth in basal medium supplemented with 2% fetal calf serum (FCS), blocked PDGF- and EGF-stimulated cell proliferation, and modulated that of HBGF-1. PDGF, but not EGF or HBGF-1, activated the inositol trisphosphate/diacylglycerol (IP3/DAG) second message system in a dose-dependent manner. EGF inhibited phosphoinositol lipid turnover and HBGF-1 and TGF-beta stimulated phosphatidylinositol hydrolysis to produce inositol phosphate (IP) but not IP3. Preincubation of quiescent cells with TGF-beta for 30-40 minutes prior to the addition of PDGF resulted in an inhibition of PDGF-induced production of IP3. This suggested that TGF-beta was an indirect inhibitor and blocked PDGF-stimulated cell growth in part by interfering with the generation of the second messenger, IP3.
Pontbriant
C M
CM
Department of Biology, Boston College, Chestnut Hill, Massachusetts 02167.
Chen
J K
JK
Orlando
J A
JA
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007700:Kinetics; D012516:Osteosarcoma; D010716:Phosphatidylinositols / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D016220:Fibroblast Growth Factor 1; D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate