COLONOCYTE DIFFERENTIATION IS ASSOCIATED WITH INCREASED EXPRESSION AND ALTERED DISTRIBUTION OF PROTEIN-KINASE-C ISOZYMES

Background & Aims: Colon cancer cells express reduced levels of protei n kinase C (PKC). This study examines the regulation of PKC isozymes i n normal colonic epithelium, as a basis for understanding the signific ance of alterations in this enzyme system in colon carcinogenesis. Met hods: The expression and localization of PKC isozymes in mouse and rat colonocytes at different developmental stages were determined using a combined morphological and biochemical approach. PKC or expression wa s compared in colonic adenocarcinomas and adjacent normal mucosa by im munoblot analysis. Results: Mouse and rat colonocytes express PKC alph a, beta II, delta, epsilon, and zeta. Relatively low levels of these i sozymes were detected in proliferating cells of the crypt base, predom inantly in the cytosolic compartment. Coincident with colonocyte growt h arrest/differentiation, PKC isozyme expression markedly increased in both the cytosolic and, more significantly, in the membrane/cytoskele tal fraction. Colonic tumors express reduced levels of PKC alpha, an i sozyme that has been implicated in negative control of intestinal cell growth. Conclusions: These findings are supportive of a role for cert ain PKC isozyme(s) in signaling pathways mediating postmitotic events in colonocytes in situ, and suggest that diminished activity of these pathway(s) may contribute to the alterations in growth control/differe ntiation associated with colonic neoplasia.