PROTEIN-KINASE-C ISOFORM EXPRESSION AND FUNCTION IN TRANSFORMED AND NONTRANSFORMED PANCREATIC ACINAR CELL-LINES

Members of the protein kinase C (PKC) family of multifunctional serine /threonine phosphorylating enzymes are believed to play a role in regu lating cellular differentiation and proliferation in many cell types. In the present study, we examined the expression of PKC isoforms in no n-transformed (BMRPA.430) and transformed (TUC3) rat pancreatic acinar cell lines and compared this to PHC expression in freshly dispersed a cini from rat pancreas. BMRPA.430 cells maintain characteristics of no rmal acini and are not tumorigenic, whereas TUC3 cells do trot express tight junctions or polygonal morphology and are tumorigenic. As repor ted previously, PKC alpha, delta, epsilon, and zeta are expressed in f reshly prepared acini. Likewise, these isoforms were detected in both the BMRPA.430 and TUC3 cell lines. In addition, PKC theta, a novel iso form, was detected in all three cell types sat low levels. We used two PKC inhibitors to examine the role of PKC in acinar cell proliferatio n. CGP 41 251, a selective PKC inhibitor; and Go 6976, an agent which specificality inhibits calcium-dependent PKC isoforms, inhibited cell proliferation of both cell lines. Translocation of PKC alpha to the me mbrane was not observed in either cell Line. Hence, our data indicate that ras-induced transformation does nest alter PKC isoform expression in pancreatic acinar cells and that activation of PKC alpha is involv ed with acinar cell growth. (C) 1998 Academic Press.