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 PKCδ and cytosolic PKCβ decreased, whereas the expression of the other isoforms was not altered. After a 13-week chronic exposure, membrane-bound PKCβ, δ and ζ levels decreased. In WY-induced hepatocellular adenomas, PKCα was increased, and PKCβ was further decreased in membrane fractions. These results, taken together with previous studies, indicate that alterations in PKCα, β and δ isoforms, which regulate mitogenesis, could play important roles in perpetuating the high cell proliferative rate in PPC-induced hepatocellular adenomas.