Inhibition of protein kinase C is associated with a decrease in c-myc expression in human myeloid leukemia cells

• Published in: FEBS letters 1991-12, Vol.294 (1), p.73-76
• Main Authors: Bernstein, Steven H., Kharbanda, Surender M., Sherman, Matthew L., Stone, Richard M., Kufe, Donald W.
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Alkaloids - pharmacology; Biological and medical sciences; Blotting, Northern; c-Myc; Cell Line; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation, Neoplastic - drug effects; genes; Genes, myc - drug effects; Humans; Isoquinolines - pharmacology; Kinetics; Leukemia, Myeloid; Molecular and cellular biology; Molecular genetics; myeloid leukemia; phorbol 12-myristate 13-acetate diester; Piperazines - pharmacology; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Pyrimidine Nucleosides - pharmacology; RNA, Messenger - genetics; RNA, Neoplasm - genetics; RNA, Neoplasm - isolation & purification; Staurosporine; Sulfonamides; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(91)81346-A

Treatment of human myeloid leukemic cells with phorbol esters such as 12- O-tetradecanoylphorbol-13-acetate (TPA) is associated with activation and then partial down-regulation of protein kinase C activity. Previous work has suggested that the activation of protein kinase C by TPA contributes to the decrease in c-myc expression during differentiation of these cells. The present studies demonstrate that the decline in c-myc mRNA levels following exposure of HL-60 cells to TPA is preceded by an increase in expression of this gene. In contrast, exposure of HL-60 cells to inhibitors of protein kinase C activity is associated with down-modulation of c-myc expression. Similar findings have been obtained in U-937 myeloid leukemia cells. Taken together, these findings suggest that phorbol esters have a biphasic effect on c-myc expression. Whereas the activation of protein kinase C by phorbol esters may be associated with an increase in c-myc gene expression, the subsequent partial down-regulation of kinase activity may initiate a cascade of events resulting in the down-modulation of c-myc expression.