Alteration of protein kinase C isoform-specific expression during rat hepatocarcinogenesis after exposure to the peroxisome proliferator WY-14,643

The role of protein kinase C (PKC) isoforms in mediating peroxisome proliferator chemical- (PPC) induced hepatocarcinogenesis was examined. After an acute gavage exposure to WY-14,643 (WY) membrane-bound PKC delta and cytosolic PKC beta decreased, whereas the expression of the other isoforms was not altered. After a 13-week chronic exposure, membrane-bound PKC beta, delta and zeta levels decreased. In WY-induced hepatocellular adenomas, PKC alpha was increased, and PKC beta was further decreased in membrane fractions. These results, taken together with previous studies, indicate that alterations in PKC alpha, beta and delta isoforms, which regulate mitogenesis, could play important roles in perpetuating the high cell proliferative rate in PPC-induced hepatocellular adenomas. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.