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Inhibition of protein kinase C is associated with a decrease in c-myc expression in human myeloid leukemia cells.
S H Bernstein1, S M Kharbanda, M L Sherman
1Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, MA.
FEBS Letters
|December 2, 1991
Summary
Phorbol esters like 12-O-tetradecanoylphorbol-13-acetate (TPA) initially increase, then decrease, c-myc gene expression in leukemia cells. This biphasic effect on c-myc is linked to protein kinase C activity changes during cell differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), modulate protein kinase C (PKC) activity in myeloid leukemic cells.
- Previous studies linked PKC activation by TPA to decreased c-myc expression during cellular differentiation.
Purpose of the Study:
- To investigate the biphasic effect of phorbol esters on c-myc gene expression in human myeloid leukemic cells.
- To elucidate the role of protein kinase C activity in regulating c-myc expression.
Main Methods:
- Exposure of HL-60 and U-937 myeloid leukemia cells to TPA.
- Treatment with protein kinase C inhibitors.
- Analysis of c-myc mRNA levels and gene expression.
Main Results:
- TPA treatment initially increased, then decreased, c-myc mRNA levels in HL-60 cells.
- Inhibition of PKC activity led to down-modulation of c-myc expression.
- Similar biphasic regulation of c-myc was observed in U-937 cells.
Conclusions:
- Phorbol esters exert a biphasic influence on c-myc expression in myeloid leukemia cells.
- PKC activation may initially upregulate c-myc, while subsequent PKC down-regulation triggers c-myc downregulation.
- These findings highlight PKC's complex role in c-myc regulation during myeloid differentiation.