DIFFERENTIAL PHORBOL ESTER GROWTH MODULATION AND PROTEIN-KINASE-C ISOENZYME EXPRESSION IN RAT HEPATOMA-CELLS VS NON NEOPLASTIC RAT HEPATOCYTES

In the present study the expression of protein kinase C (PKC) isoenzymes and the growth modulation caused by phorbol esters were studied in two rat hepatic cell lines: the neoplastic MH1C1 hepatoma and the syngeneic immortalized non-neoplastic BRL3A cell line. Western blot analysis revealed that MH1C1 rat hepatoma cells express the a isoenzyme as the only isoform of PKC, whereas BRL3A cells showed immunoreactivity for alpha, delta and epsilon PKC. Immunoblot analysis showed that in both cell lines phorbol 12-myristate 13-acetate (PMA) caused a persistent, marked down-regulation of all expressed PKC isoenzymes. In MH1C1 cells, PMA also induced a reversible, marked dose-dependent growth inhibition, whereas a minimal impairment of cell proliferation was observed in BRL cells. The observed selective mitoinhibitory effect of PMA on tumor cells indicates PKC as an interesting target for innovative antiproliferative strategies based on the modulation of specific isoenzymes.