Differential inhibitory effects of TGF-beta on EGF-, PDGF-, and HBGF-1-stimulated MG63 human osteosarcoma cell growth: possible involvement of growth factor interactions at the receptor and postreceptor levels.
The growth of MG63 human osteosarcoma cell line in 5% serum is stimulated by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or heparin-binding growth factor-1 (HBGF-1). The mitogenic effect of EGF and PDGF is completely blocked by TFG-beta at 1 ng per ml and the effect of HBGF-1 is attenuated by 75-80%. Treatment of MG63 cells with TGF-beta reduces HBGF-1 receptor binding affinity from 1.24 x 10(-11) M to 3.51 x 10(-11) M with no change on the receptor number (1.1 x 10(3) per cell). The receptor-binding affinity of EGF and PDGF is not altered by TGF-beta treatment; however, the number of EGF receptor is increased by 25%. Both EGF and PDGF stimulate MG63 cellular tyrosine kinase activity, and such stimulation is inhibited by TGF-beta pretreatment. No change in the cellular protein tyrosine phosphorylation pattern can be detected in HBGF-1-stimulated cells with and without TGF-beta pretreatment. These data suggest that TGF-beta inhibits EGF and PDGF mitogenicity by blocking EGF- and PDGF-stimulated tyrosine kinase activity and attenuates HBGF-1 mitogenicity by decreasing its receptor affinity.
Mioh
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W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.
Chen
J K
JK
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D016220:Fibroblast Growth Factor 1; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008934:Mitogens / Q000494:pharmacology*; D008970:Molecular Weight; D012516:Osteosarcoma; D010750:Phosphoproteins / Q000302:isolation & purification; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011975:Receptors, Mitogen / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D006133:Growth Substances; D008934:Mitogens; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011975:Receptors, Mitogen; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D006493:Heparin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor