Increased activity and expression of MAP kinase in HCC model rats induced by 3'-methyl-4-dimethylamino-azobenzene.
OBJECTIVE
The ras-mitogen-activated protein kinase (MAPK) cascade plays an important role not only in the mitogenic signal transduction pathway but also in the development of cancer, and it is believed to be one of the important regulators in normal hepatocytes and hepatocellular carcinoma. The aim of this study was to determine the role of insulin receptor substrate-1 and the MAPK cascade in rats with hepatocellular carcinoma induced by 3'-methyl-4-dimethylamino-azobenzene (3'-MeDAB).


METHODS
Liver cancer was induced in rats by feeding 3'-MeDAB, and the changes in expression of IRS-1 and MAPK were analyzed in tumorous, non-tumorous and control liver.


RESULTS
Expression of insulin receptor substrate-1 (IRS-1) showed a 1.4-fold increase at protein level in the tumors (p<0.01), but the tyrosine phosphorylation of IRS-1 did not differ between the tumor and control liver. Expression of MAPK and its activity were elevated 4.5-7.5-fold (p<0.01) and 4.6-fold (p<0.01) in the tumor compared with control liver. In non-tumorous lesions from rats fed with 3'-MeDAB, expression of MAPK, but not IRS-1, increased significantly (p<0.01). Between tumorous and adjacent non-tumorous lesions, there was a significant difference in MAPK expression (p<0.05) and activities (p<0.05).


CONCLUSIONS
The increased expression of MAPK may play an important role in the progression or initiation of HCC in this rat model.
Toyoda
M
M
The Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Hashimoto
N
N
Tokita
K
K
Goldstein
B J
BJ
Yokosuka
O
O
Kanatsuka
A
A
Suzuki
Y
Y
Saito
Y
Y
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000031:analogs & derivatives*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014443:Tyrosine / Q000378:metabolism
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; C032237:3'-hydroxymethyl-4-(dimethylamino)azobenzene; D014443:Tyrosine; D008749:Methyldimethylaminoazobenzene; D020928:Mitogen-Activated Protein Kinases