Studies on protein kinase C and colon carcinogenesis
J. G. Guillem, C. A. O'Brian, C. J. Fitzer, M. D. Johnson, K. A. Forde, P. LoGerfo and I. B. Weinstein
Department of Surgery, Columbia-Presbyterian Medical Center, Columbia University, New York, NY 10032.
To further understand the molecular mechanisms of bile acid-mediated colon
tumor promotion, we have examined the possible role of protein kinase C
(PKC) in this process. Protein kinase C has been implicated in tumor
promotion because it is the receptor for the tumor promoter
12-0-tetradecanoyl-phorbol-13-acetate (TPA) and mediates the action of this
compound as well as that of other tumor promoters and growth factors. Our
studies show that, in a manner analogous to
12-0-tetradecanoyl-phorbol-13-acetate, deoxycholic acid (DOA) can induce a
time-dependent cellular redistribution of PKC as well as a
concentration-dependent overexpression of the ornithine decarboxylase gene.
These results taken together with our previous findings demonstrating
decreased levels of PKC in human colon carcinomas compared with adjacent
normal mucosa provide evidence that PKC has a role in colon carcinogenesis.
