Selective modulation of protein kinase A and protein kinase C activities in epidermal growth factor (EGF)-stimulated MCF-7 breast cancer cells

Biol Chem. 1997 Sep;378(9):1023-9. doi: 10.1515/bchm.1997.378.9.1023.

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