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

Prostaglandins Other Lipid Mediat. 2013 Oct:106:106-15. doi: 10.1016/j.prostaglandins.2013.03.006. Epub 2013 Apr 8.

Abstract

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.

Keywords: Biomarkers; COX-2; HCC; PGE(2); Transgenic mice; c-myc/TGF-α model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cyclooxygenase 2 / genetics*
  • Disease Progression
  • Female
  • Gene Expression
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-myc / genetics*
  • Signal Transduction / genetics
  • Transforming Growth Factor alpha / genetics*

Substances

  • Proto-Oncogene Proteins c-myc
  • Transforming Growth Factor alpha
  • Cyclooxygenase 2