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Inhibition of protein kinase C is associated with a decrease in c‐myc expression in human myeloid leukemia cells
Author(s) -
Bernstein Steven H.,
Kharbanda Surender M.,
Sherman Matthew L.,
Stone Richard M.,
Kufe Donald W.
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)81346-a
Subject(s) - protein kinase c , myeloid leukemia , myeloid , phorbol ester , protein kinase a , microbiology and biotechnology , tetradecanoylphorbol acetate , phorbol , kinase , leukemia , biology , chemistry , gene expression , cancer research , gene , biochemistry , immunology
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.