Alteration of protein kinase C isoform-specific expression during rat hepatocarcinogenesis after exposure to the peroxisome proliferator WY-14,643.
The role of protein kinase C (PKC) isoforms in mediating peroxisome proliferator chemical- (PPC) induced hepatocarcinogenesis was examined. After an acute gavage exposure to WY-14,643 (WY) membrane-bound PKCdelta and cytosolic PKCbeta decreased, whereas the expression of the other isoforms was not altered. After a 13-week chronic exposure, membrane-bound PKCbeta, delta and zeta levels decreased. In WY-induced hepatocellular adenomas, PKCalpha was increased, and PKCbeta was further decreased in membrane fractions. These results, taken together with previous studies, indicate that alterations in PKCalpha, beta and delta isoforms, which regulate mitogenesis, could play important roles in perpetuating the high cell proliferative rate in PPC-induced hepatocellular adenomas.
Corton
J C
JC
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709-2137, USA. corton@ciit.org
Swanson
C
C
Miller
R T
RT
Cattley
R C
RC
D000236:Adenoma / Q000139:chemically induced / Q000201:enzymology; D000818:Animals; D002273:Carcinogens; D002725:Chloroform / Q000633:toxicity; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011743:Pyrimidines; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011743:Pyrimidines; D002725:Chloroform; C006253:pirinixic acid; D011493:Protein Kinase C