Altered levels of protein kinase C and Ca2+-dependent protein kinases in human colon carcinomas.
Protein kinase C (PKC) is a Ca2+- and phospholipid-dependent protein kinase which is implicated in tumor promotion, since it has been demonstrated to be a high affinity receptor for tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate. Colon carcinogenesis appears to proceed through distinct stages of initiation and promotion. The present studies show that PKC and calcium-dependent protein kinase specific activities are reduced in human colon carcinomas when compared to their normal adjacent colon mucosa. There were significantly higher Ca2+-dependent protein kinase and PKC specific activities observed in both the cytosolic and particulate fractions of the normal mucosa relative to the corresponding values obtained with the carcinoma fractions. The average specific activity ratios were 5.1 (normal cytosolic/carcinoma cytosolic) and 3.7 (normal particulate/carcinoma particulate) for PKC. PKC activity was reduced in the carcinoma tissues with respect to both protein and tissue weight. The percentage of Ca2+-dependent protein kinase and PKC activities that were present in the particulate fraction of each of the samples varied considerably among tissues, and in general there was no systematic difference between the carcinoma and normal mucosa samples. However, in the carcinoma samples that contained an extensive admixture of benign adenomatous tissue, the particulate fractions consistently contained greater than 60% of the total Ca2+-dependent protein kinase and PKC activities. The present studies indicate that colon carcinogenesis is associated with alterations in cellular levels of protein kinase activities.
D002118:Calcium / Q000494:pharmacology*; D002277:Carcinoma / Q000201:enzymology*; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D011493:Protein Kinase C / Q000032:analysis*; D011494:Protein Kinases / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium