Mitogenic growth factors regulate differentially early gene mRNA expression: a study on two clones of 3T3 fibroblasts.
The relationship between cell proliferation and mRNA levels of the immediate early genes c-fos, c-jun, and jun B has been investigated in two clones of 3T3 fibroblasts (D1-3T3 and N2-3T3) upon treatment with basic fibroblast growth factor (bFGF), thrombin, phorbol 12-myristate 13-acetate (PMA) and dibutyryl cyclic AMP (Bt2cAMP). The 3T3-derived clone D1-3T3 almost stops dividing upon serum deprivation, while the N2-3T3 clone does not. The proliferation of the two clones was stimulated by thrombin and PMA and inhibited by Bt2cAMP. Basic FGF stimulated the growth of D1-3T3 but partly inhibited that of N2-3T3 cells. In spite of variable mitogenic response, immediate early genes, c-fos, c-jun, jun B, and c-myc, were induced by the growth factors and by PMA in both cell clones. In our experimental conditions the early gene mRNAs were expressed independently; i.e., the expression of one protooncogene had no bearing on the expression of the other. The cell growth was not directly related to the expression of a particular protooncogene mRNA. Data are presented showing that early gene mRNA expression induced by bFGF or thrombin was not mediated by protein kinase C activation while thrombin-induced mitosis was. Basic FGF induced a part of c-jun mRNA expression, but not mitosis, through a pertussis toxin-sensitive mechanism.
Janet
T
T
Laboratoire de Neurobiologie Ontogénique, CNRS UPR 417, Strasbourg, France.
Labourdette
G
G
Sensenbrenner
M
M
Pettmann
B
B
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D051379:Mice; D037342:Pertussis Toxin; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D010566:Virulence Factors, Bordetella; D016222:Fibroblast Growth Factor 2; D003994:Bucladesine; D037342:Pertussis Toxin; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium