ϵPKC Acts Like a Marker of Progressive Malignancy in Rat Liver, but Fails to Enhance Tumorigenesis in Rat Hepatoma Cells in Culture

We have analyzed the expression pattern of epsilon protein kinase C (PKC) in normal liver tissue, in hyperplastic liver nodules and in hepatocellular carcinomas generated in the rat with the Solt-Farber protocol. A progressive increase in PKC epsilon expression was observed in nodules and carcinomas compared to normal liver tissue, suggesting that the expression level of this PKC isoenzyme could be associated with increased malignancy. To test this hypothesis, the well differentiated, poorly tumorigenic MH1C1 rat hepatoma cell line was stably transfected with a full length epsilon PKC cDNA. No increase in growth rate, saturation density, soft agar growth or in vivo tumorigenicity was observed in transfected cells, compared to parental or mock-transfected cells. These results indicate that epsilon PKC does not seem to participate in signaling pathways involved in neoplastic transformation or malignant progression in our liver cell model. The fact that epsilon PKC overexpression is tumorigenic in several other cell types suggests that this effect might be strictly cell- and tissue-specific. (C) 1996 Academic Press, Inc.