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) isoenzym es and the growth modulation caused by phorbol esters were studied in two rat hepatic cell lines: the neoplastic MH1C1 hepatoma and the syng eneic immortalized non-neoplastic BRL3A cell line. Western blot analys is revealed that MH1C1 rat hepatoma cells express the a isoenzyme as t he only isoform of PKC, whereas BRL3A cells showed immunoreactivity fo r alpha, delta and epsilon PKC. Immunoblot analysis showed that in bot h cell lines phorbol 12-myristate 13-acetate (PMA) caused a persistent , marked down-regulation of all expressed PKC isoenzymes. In MH1C1 cel ls, PMA also induced a reversible, marked dose-dependent growth inhibi tion, whereas a minimal impairment of cell proliferation was observed in BRL cells. The observed selective mitoinhibitory effect of PMA on t umor cells indicates PKC as an interesting target for innovative antip roliferative strategies based on the modulation of specific isoenzymes .