Abstract
In human MCF-7 breast cancer cells, both protein kinase A (PKA) and different members of the protein kinase C (PKC) family are stimulated upon binding of epidermal growth factor (EGF) to cell surface receptors. Selective stimulation of calcium-dependent PKCs with 10(-6) to 10(-9) M Thymeleatoxin significantly increased the proliferation rate of MCF-7 cells over 5 days in culture. This stimulation was blocked by the PKC antagonist Chelerythrine. In contrast, selective activation of PKA by addition of 1 mM dibutyryl cyclic AMP (dBcAMP) did not affect the proliferation rate of MCF-7 cells. Similarly, activation of the adenylate cyclase by 1 microM Forskolin and inhibition of PKA by the cyclic AMP analogue Rp-cAMPS did not modulate the proliferation rate of these cells. Activation of PKC stimulated the expression of the immediate early gene c-fos but c-myc expression was not significantly enhanced. On the other hand, PKA activation increased both c-myc and c-fos expression in MCF-7 cells. These results suggest that PKA activation and c-myc expression are not obligatory for proliferation of MCF-7 cells.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alkaloids
-
Benzophenanthridines
-
Blotting, Northern
-
Breast Neoplasms / metabolism*
-
Breast Neoplasms / pathology
-
Bucladesine / pharmacology
-
Cell Division / drug effects
-
Colforsin / pharmacology
-
Cyclic AMP-Dependent Protein Kinases / analysis
-
Cyclic AMP-Dependent Protein Kinases / chemistry
-
Cyclic AMP-Dependent Protein Kinases / metabolism*
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology
-
Epidermal Growth Factor / pharmacology*
-
Female
-
Gene Expression Regulation / drug effects
-
Genes, fos / drug effects
-
Genes, fos / genetics
-
Genes, myc / drug effects
-
Genes, myc / genetics
-
Humans
-
Phenanthridines / pharmacology
-
Phorbol Esters / pharmacology
-
Protein Kinase C / antagonists & inhibitors
-
Protein Kinase C / chemistry
-
Protein Kinase C / metabolism*
-
Receptors, Cell Surface / drug effects*
-
Receptors, Cell Surface / metabolism
-
Tumor Cells, Cultured / drug effects
-
Tumor Cells, Cultured / enzymology
Substances
-
Alkaloids
-
Benzophenanthridines
-
Enzyme Inhibitors
-
Phenanthridines
-
Phorbol Esters
-
Receptors, Cell Surface
-
Colforsin
-
Epidermal Growth Factor
-
Bucladesine
-
thymeleatoxin
-
chelerythrine
-
Cyclic AMP-Dependent Protein Kinases
-
Protein Kinase C