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.