Involvement of two intracellular messenger systems, protein kinase C and cyclic AMP, in the regulation of c-fos gene expression in human promyelocytic leukemia (HL-60) cells.
Incubation of human promyelocytic leukemia (HL-60) cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a protein kinase C-activating phorbol ester, caused a marked increase in c-fos mRNA in a dose-dependent manner. Phorbol-12,13-dibutyrate and 1-oleoyl-2-acetyl-glycerol, other protein kinase C-activating agents, were also active in this capacity. 4 alpha-Phorbol-12,13-didecanoate, known to be inactive for protein kinase C, was ineffective. 8-Bromo-cyclic AMP (8-Br-cAMP) also increased c-fos mRNA in a dose-dependent manner. This action of 8-Br-cAMP was mimicked by prostaglandin E2, which is known to raise the cyclic AMP level in HL-60 cells. c-fos mRNA increased within 15 min and reached a maximal level 45 min after the stimulation of the cells by TPA or 8-Br-cAMP. The simultaneous stimulation of the cells by TPA and 8-Br-cAMP at the respective doses giving maximal elevation of c-fos mRNA increased this mRNA in an additive manner. These results suggest that in HL-60 cells expression of the c-fos gene is regulated independently by two different intracellular messenger systems, protein kinase C and cyclic AMP.
Tsuda
T
T
Department of Biochemistry, Kobe University School of Medicine, Hyogo.
Fukumoto
Y
Y
Hamamori
Y
Y
Yamashita
T
T
Takai
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D010703:Phorbol Esters; D011458:Prostaglandins E; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; C038237:1-oleoyl-2-acetylglycerol; D000242:Cyclic AMP; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate