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Altered Levels of Protein Kinase C and Ca²⁺-dependent Protein Kinases in Human Colon Carcinomas¹

Department of Surgery, Columbia-Presbyterian Medical Center [J. G. G., K. A. F., P. L., M. T.], Division of Environmental Sciences and Institute of Cancer Research [C. A. O., C. J. F., I. B. W.], Columbia University, New York, New York 10032

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.

¹ This work was supported by National Cancer Institute Grant CA2-6056-02 and the Jean and Louis Dreyfus Foundation.

² Supported by the Phyllis Jacobs Rubenstein-Arthur Jacobs Fellowship in Surgical Oncology. To whom requests for reprints should be addressed.

Received 10/ 1/86. Revised 12/ 9/86. Accepted 1/16/87.

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