Platelet-derived growth factor-induced c-myc RNA expression. Analysis of an inducible pathway independent of protein kinase C.
Platelet-derived growth factor (PDGF) is generally considered to stimulate phosphoinositide turnover resulting in activation of protein kinase C and increased cytoplasmic [Ca2+]. We have examined the role of these secondary effects in regulation of c-myc mRNA accumulation in the MG-63 human osteogenic sarcoma line. Treatment of quiescent cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) to down-regulate protein kinase C inhibited TPA-stimulated c-myc expression but did not affect the PDGF-modulated process. When cytoplasmic [Ca2+] was increased by addition of a Ca2+ ionophore (A23187 or ionomycin), no stimulation of c-myc RNA was seen; furthermore, these agents did not enhance the PDGF-modulated c-myc expression. Addition of EGTA to cultures treated with both PDGF and a Ca2+ ionophore did not inhibit c-myc induction but rather caused a superinduction of c-myc RNA accumulation. Superinduction occurred only if the [EGTA] was greater than [Ca2+] in the medium. This superinduction was distinct from the increased induction caused by inhibition of protein synthesis. Because PDGF-induced c-myc expression is independent of protein kinase C and increased cytoplasmic [Ca2+], the evidence suggests that PDGF modulates c-myc RNA accumulation in MG-63 cells via a novel pathway, seemingly uncoupled from the classic action of increased phosphoinositide metabolism.
D000001:Calcimycin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015759:Ionomycin; D009857:Oncogenes; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D004987:Ethers; D010972:Platelet Activating Factor; D000001:Calcimycin; D004533:Egtazic Acid; D015759:Ionomycin; D012313:RNA; D003513:Cycloheximide; D011493:Protein Kinase C