EXPRESSION OF PROTEIN-KINASE-C ISOENZYMES IN COLORECTAL-CANCER TISSUEAND THEIR DIFFERENTIAL ACTIVATION BY DIFFERENT BILE-ACIDS

Expression of protein kinase C (PKC) isoenzymes was determined in pair ed samples of normal mucosa and colorectal cancer tissue from 13 patie nts. Total PKC activity in cancer tissue was significantly decreased c ompared to that in normal mucosa. Western blotting, using PKC isoenzym e-specific antibodies, showed that two PKC isoenzymes, PKC beta and PK C epsilon, were significantly decreased in cancer tissue. The level of PKC delta was increased in cancer tissue and the expression of PKC al pha and zeta 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 ursodeo xycholic acid (UDCA)-were found to be potent and selective activators of partially purified PKC isoenzymes. PKC beta 1 was the isoenzyme mos t effectively activated by secondary bile acids. Our data provide a mo del for the involvement of secondary bile acids in colorectal carcinog enesis through specific PKC isoenzyme modulation in colorectal mucosa. (C) 1995 Wiley-Liss, Inc.