Basic fibroblast growth factor: production, mitogenic response, and post-receptor signal transduction in cultured normal and transformed fetal bovine aortic endothelial cells.
Normal FBAE AG 7680 cells and chemically transformed FBAE GM 7373 cells were compared for their capacity to produce and to respond to bFGF. Normal FBAE cells showed higher levels of bFGF protein and of poly(A)+ bFGF mRNA than transformed GM 7373 cells, indicating that chemical transformation in FBAE cells is paralleled by a decrease of bFGF gene expression. Basic FGF induced cell proliferation in both normal and transformed FBAE cells. However, bFGF appeared to be much more potent in transformed than in normal cells. No differences in bFGF membrane receptors were observed between normal and transformed FBAE cells in terms of apparent molecular weight, number per cell, dissociation constant, and kinetic of downregulation. In respect to normal cells, however, transformed GM 7373 cells showed higher basal levels of PKC activity. This kinase is activated by bFGF and is involved in mediating the mitogenic activity of bFGF, as shown by the capacity of the PKC inhibitor H-7 to abolish the mitogenic activity of bFGF both in normal and transformed FBAE cells. Like bFGF, the PKC activators DAG and TPA exerted a stronger mitogenic activity in transformed than in normal FBAE cells. Thus, the different susceptibility of normal and transformed FBAE cells to bFGF appears to depend on differences in the post-receptor signal transduction mediated by PKC rather than on differences in bFGF receptors. The results indicate that chemical transformation causes significant modifications of bFGF physiology in FBAE cells. The relevance of these modifications to the genesis of tumors of vascular origin deserves further investigation.
Presta
M
M
Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy.
Maier
J A
JA
Rusnati
M
M
Ragnotti
G
G
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011493:Protein Kinase C / Q000494:pharmacology / Q000502:physiology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D011493:Protein Kinase C