Activation by phorbol esters of protein kinase C in MCF‐7 human breast cancer cells

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Abstract
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.