Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids

Abstract Expression of protein kinase C (PKC) isoenzymes was determined in paired samples of normal mucosa and colorectal cancer tissue from 13 patients. Total PKC activity in cancer tissue was significantly decreased compared to that in normal mucosa. Western blotting, using PKC isoenzyme‐specific antibodies, showed that two PKC isoenzymes, PKC β and PKC ϵ, were significantly decreased in cancer tissue. The level of PKC δ was increased in cancer tissue and the expression of PKC α and ζ was not altered significantly. Primary bile acids—cholic acid (CA) and chenodeoxycholic acid (CDCA)—and the principal secondary bile acids—deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA)—were found to be potent and selective activators of partially purified PKC isoenzymes. PKC β I was the isoenzyme most effectively activated by secondary bile acids. Our data provide a model for the involvement of secondary bile acids in colorectal carcinogenesis through specific PKC isoenzyme modulation in colorectal mucosa. © 1995 Wiley‐Liss, Inc .