Protein kinase C tissue localization in human colonic tumors suggests a role for adenoma growth control

Abstract

Background and Aims: Protein kinase C (PKC) has been implicated as a mediator of growth control during colorectal carcinogenesis, but the mechanisms involved are still a matter of dispute. The aim of this study was to analyze PKC patterns and tissue distribution to gain further insight in PKC function during tumor development in the gut. Methods: PKC isoenzymes α, β1, β2, δ, and η and the proliferation antigen Ki67 were analyzed in formalin-fixed normal, premalignant, and malignant specimens using immunohistochemistry. Results: In normal colonic mucosa, protein levels of all PKC isoenzymes followed an increasing gradient from the bottom to the top of the crypt, staining mainly terminally differentiated, resting cells. Atypical crypts observed in the normal mucosa adjacent to tumors expressed higher levels of Ca2+-dependent isoenzymes than the surrounding tissue. In tumors, the number and abundance of PKC isoenzymes was inversely related to proliferation in 7 adenomas and 9 carcinomas. Areas containing PKC-β1 as the only isoenzyme had the highest proliferation rates (50%-82% Ki67-positive cells). Conclusions: The data suggest a function of PKCs, especially PKC- β1, in colorectal carcinogenesis and tumor growth control.