Activation by phorbol esters of protein kinase C in MCF-7 human breast cancer cells.
Exposure of MCF-7 human breast cancer cells to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to the inhibition of cell proliferation. We investigate here the short-term effects of TPA on subcellular distribution of protein kinase C, and on protein phosphorylation in cultured MCF-7 cells. We report a rapid and dramatic decrease in cytosolic protein kinase C activity after TPA treatment. Only 30% of the enzymatic activity lost in the cytosol was recovered in the particulate fraction. These data suggest that subcellular translocation of protein kinase C is accompanied by a rapid down-regulation of the enzyme (70%). Furthermore, TPA and other protein kinase C activators rapidly induce the phosphorylation of a 28 kDa protein in intact MCF-7 cells. Phorbol esters devoid of tumor-promoting activity are ineffective both for inducing these early biochemical events and for inhibiting cell proliferation.
M
M
Issandou
F
F
Bayard
J M
JM
Darbon
D001943:Breast Neoplasms / Q000201:enzymology*; D002460:Cell Line; D002848:Chromatography, DEAE-Cellulose; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000032:analysis*; D011506:Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D011506:Proteins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate