Stimulation by TGF beta of chick embryo fibroblasts--inhibition by an IGFBP-3.
The multiple effects of TGF beta on cell proliferation are not well understood. Our results show that TGF beta was a good but transient mitogen for chick embryo fibroblasts. DNA synthesis was three- to fourfold increased, even at high concentrations of TGF beta. We did not show a bimodal effect. An inhibitor of cell growth, that inhibits 100% of stimulation induced by serum in CEF, was purified to homogeneity from medium conditioned by mouse 3T3 cells. This inhibitor has been shown to be an IGF-binding protein (mIGFBP-3). In the present work, this mIGFBP-3 inhibited the TGF beta stimulation by about 50%, while the stimulation induced by PDGF or insulin was not inhibited by mIGFBP-3. Furthermore, TGF beta stimulation, in the presence of a high concentration of insulin in conditions which would saturate IGF receptors, was not significantly inhibited by mIGFBP-3. All together these results suggest that a part of the mitogenic effect of TGF beta may be through increasing IGF secretion and eventually other growth factors such as PDGF (as suggested previously).
Imbenotte
J
J
Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Liu
L
L
Desauty
G
G
Harel
L
L
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013002:Somatomedins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D010982:Platelet-Derived Growth Factor; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D004247:DNA