Five of six protein kinase C isoenzymes present in normal mucosa show reduced protein levels during tumor development in the human colon.
Protein kinase C (PKC) isoenzyme patterns were analyzed from human colonic epithelial cells of normal, premalignant and malignant origin. PKCs alpha, beta and zeta were found predominantly in the cytosol and the subtypes delta, epsilon and neta almost exclusively in the particulate fraction. Of the isoenzymes found beta, epsilon and neta were low in abundance and could only be detected after partial purification of cellular fractions on DE52-cellulose. Only PKC beta 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 Ca(2+)-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 alpha, delta and to a lesser degree also beta. We assume that this reflects qualitative differences in response between normal and tumor cells, that may be due to the differences in isoenzyme distribution.
Kahl-Rainer
P
P
Institute for Tumor Biology-Cancer Research, University of Vienna, Austria.
Karner-Hanusch
J
J
Weiss
W
W
Marian
B
B
D000236:Adenoma / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology*; D004848:Epithelium / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*
D007527:Isoenzymes; D010703:Phorbol Esters; D011493:Protein Kinase C; D002118:Calcium