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).
Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
J
J
Imbenotte
L
L
Liu
G
G
Desauty
L
L
Harel
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