Effect on the expression of c-met, c-myc and PPAR-{alpha} in liver and liver tumors from rats chronically exposed to the hepatocarcinogenic peroxisome proliferator WY-14, 643

The induction of rodent hepatic tumors by peroxisome proliferators(PP) appears to depend on focal growth of hepatocytes. Expressionof the oncogenes c-met and c-mycis altered following regenerativestimuli in rat liver, suggesting involvement of their proteinproducts in hepatocyte replication. In addition, increases inc-myc and c-met mRNA expression are observed in multiple typesof human and rodent tumors, including hepatocellular carcinoma.A study was designed to test the hypothesis that developmentof PP-induced hepatic neoplasms occurs as a result of overexpressionof c-met or c-myc. Male F344 rats were exposed to WY-14, 643for 22 or 78 weeks (1000 p.p.m. in the diet). Messenger RNAwas extracted from liver tumors (78 weeks) and surrounding non-lesionliver of exposed rats and non-lesion liver from age-matchedcontrol rats. Levels of mRNA expression were compared usingNorthern analysis. Significant increases in c-met (