Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids.
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 beta and PKC epsilon, were significantly decreased in cancer tissue. The level of PKC delta was increased in cancer tissue and the expression of PKC alpha 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 ursodeoxycholic acid (UDCA)--were found to be potent and selective activators of partially purified PKC isoenzymes. PKC beta 1 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.
Pongracz
J
J
Department of Immunology, University of Birmingham, UK.
Clark
P
P
Neoptolemos
J P
JP
Lord
J M
JM
D001647:Bile Acids and Salts / Q000494:pharmacology*; D003106:Colon / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism*; D012007:Rectum / Q000201:enzymology
D001647:Bile Acids and Salts; D007527:Isoenzymes; D011493:Protein Kinase C