Progression of liver oncogenesis in the double transgenic mice c-myc/TGF α is not enhanced by cyclooxygenase-2 expression

• We examined the role of prostaglandins in hepatocarcinogenesis in an animal model of genetically induced liver tumors.
• A functional COX-2 transgene in liver did not contribute to enhanced HCC development and onset by c-myc/TGF-α.
• COX-2-dependent prostaglandin synthesis in liver has a minor contribution to liver oncogenesis.

Cyclooxygenase-2 (COX-2) has been associated with cell growth regulation, tissue remodeling and carcinogenesis. Overexpression of COX-2 in hepatocytes constitutes an ideal condition to evaluate the role of prostaglandins (PGs) in liver pathogenesis. The effect of COX-2-dependent PGs in genetic hepatocarcinogenesis has been investigated in triple c-myc/transforming growth factor α (TGF-α) transgenic mice that express human COX-2 in hepatocytes on a B6CBAxCD1xB6DBA2 background. Analysis of the contribution of COX-2-dependent PGs to the development of hepatocarcinogenesis, evaluated in this model, suggested a minor role of COX-2-dependent prostaglandins to liver oncogenesis as indicated by liver histopathology, morphometric analysis and specific markers of tumor progression. This allows concluding that COX-2 is insufficient for modifying the hepatocarcinogenesis course mediated by c-myc/TGF-α.