Effect of basic fibroblast growth factor on ornithine decarboxylase activity and mRNA expression in a pancreatic tumoral cell line (AR4-2J).
Basic fibroblast growth factor (bFGF) is a potent mitogen for various cell types. Induction of ornithine decarboxylase (ODC) activity is one of the early events triggered in proliferating cells. Our aim was to study the effect of bFGF on ODC activity and ODC mRNA expression in a pancreatic tumoral cell line, AR4-2J. Following kinetic and dose-response studies, we found that maximal stimulation (150% over control) of ODC activity occurred after 3 h of bFGF treatment (10(-9) M), the EC50 being 20 pM. To elucidate the mechanism by which bFGF stimulates ODC activity, we measured the ODC mRNA levels by Northern blot hybridization using a 32P-labeled rat cDNA probe. In AR4-2J cells treated with bFGF at 10(-9) M over 120 min, ODC mRNA expression was transiently increased by 71.6% at 60 min. Furthermore, bFGF was also able to stimulate ODC mRNA synthesis in the presence of cycloheximide. In conclusion, in AR4-2J cells of pancreatic origin, bFGF stimulates ODC gene transcription. This effect contributes to the stimulation of ODC enzymatic activity and to the proliferative effect of bFGF on this cell line.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007700:Kinetics; D009955:Ornithine Decarboxylase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D014176:Protein Biosynthesis; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D012313:RNA; D003513:Cycloheximide; D009955:Ornithine Decarboxylase