PROTEIN-KINASE-C TISSUE LOCALIZATION IN HUMAN COLONIC TUMORS SUGGESTSA ROLE FOR ADENOMA GROWTH-CONTROL

Background & Aims: Protein kinase C (PKC) has been implicated as a med iator of growth control during colorectal carcinogenesis, but the mech anisms involved are still a matter of dispute. The aim of this study w as to analyze PKC patterns and tissue distribution to gain further ins ight in PKC function during tumor development in the gut. Methods: PKC Isoenzymes alpha, beta 1, beta 2, delta, and eta and the proliferatio n antigen Ki67 were analyzed in formalin-fixed normal, premalignant, a nd malignant specimens using immunohistochemistry. Results: In normal colonic mucosa, protein levels of all PKC isoenzymes followed an incre asing gradient from the bottom to the top of the crypt, staining mainl y terminally differentiated, resting cells. Atypical crypts observed i n the normal mucosa adjacent to tumors expressed higher levels of Ca2-dependent isoenzymes than the surrounding tissue. In tumors, the numb er and abundance of PKC isoenzymes was inversely related to proliferat ion in 7 adenomas and 9 carcinomas, Areas containing PKC-beta 1 as the only isoenzyme had the highest proliferation rates (50%-82% Ki67-posi tive cells). Conclusions: The data suggest a function of PKCs, especia lly PKC-beta 1, in colorectal carcinogenesis and tumor growth control.