Possible involvement of cyclic AMP and calcium ion in prostaglandin E1-induced elevation of c-myc mRNA levels in Swiss 3T3 fibroblasts.
Prostaglandin E1 (PGE1) caused a rapid and dose-dependent increase in cAMP levels, followed by elevation of c-myc mRNA levels and then increased DNA synthesis in quiescent cultures of Swiss 3T3 fibroblasts. The dose-response curves of PGE1 were nearly the same for each of these three processes. Both 8-bromo-cAMP and forskolin increased c-myc mRNA levels to 40-50% and DNA synthesis to 70-80% of those caused by a maximally effective dose of PGE1. Under the comparable conditions, PGE1 did not stimulate diacylglycerol formation or activate protein kinase C. However, PGE1 did elevate cytoplasmic free Ca2+ concentration as measured with the fluorescent Ca2+ indicator quin 2. 8-Bromo-cAMP and forskolin were inactive in this capacity. The Ca2+ ionophore A23187 increased the level of c-myc mRNA. Diacylglycerol and Ca2+ mediate the elevation of c-myc mRNA levels which is caused by platelet-derived growth factor and fibroblast growth factor (Kaibuchi, K., Tsuda, T., Kikuchi, A., Tanimoto, T., Yamashita, T., and Takai, Y. (1986) J. Biol. Chem. 261, 1187-1192). In contrast, the present results suggest that both cAMP and Ca2+ are involved in this PGE1-induced response in Swiss 3T3 cells.
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009857:Oncogenes / Q000187:drug effects*; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D000242:Cyclic AMP; D000527:Alprostadil; D002118:Calcium