Selective modulation of protein kinase A and protein kinase C activities in epidermal growth factor (EGF)-stimulated MCF-7 breast cancer cells.
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.
Mueller
H
H
Dept. of Gynecology, School of Medicine, University Hospital Basel, and Stiftung Tumorbank Basel, Switzerland.
Liu
R
R
David
F
F
Eppenberger
U
U
D000470:Alkaloids; D053119:Benzophenanthridines; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects / Q000235:genetics; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics; D006801:Humans; D010617:Phenanthridines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D010703:Phorbol Esters; D011956:Receptors, Cell Surface; D005576:Colforsin; D004815:Epidermal Growth Factor; D003994:Bucladesine; C080287:thymeleatoxin; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C