Five of six protein kinase C isoenzymes present in normal mucosa show reduced protein levels during tumor development in the human colon

Abstract

Protein kinase C (PKC) isoenzyme patterns were analyzed from human colonic epitbelial cells of normal, premalignant and malignant origin. PKCs α, β and Ζ were found predominantly in the cytosol and the subtypes δ, ∈ and η almost exclusively in the particulate fraction. Of the isoenzymes found β, ∈ and η were low in abundance and could only be detected after partial purification of cellular fractions onDE52-.cellulose. Only PKC β was similar in abundance in normal mucosa, premalignant and malignant colonic epithelial cells, while all other isoenzymes were decreased in abundance in tumor cells. The loss of PKC protein in tumor cells correlated with a loss in enzyme activity, as has been described before by other groups, especially affecting the Ca²⁺-dependent isoenzymes. On the other hand, activation of PKC by phorbol ester treatment in vivo was only possible in carcinoma cells (4/4) and a subset of adenomas (3/7). Normal human colonic epithelial cells did not respond to TPA treatment with either stimulation of PKC activity or translocation of cytosolic enzymes to the particulate fraction. Instead, TPA treatment resulted in a rapid loss of protein for the isoenzymes α, δ and to a lesser degree also β. We assume that this reflects qualitative differences in response between normal and tumor cells, that may be due to the differences in isoenzyme distribution.