Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice

Carcinogenesis. 2007 May;28(5):940-6. doi: 10.1093/carcin/bgl249. Epub 2006 Dec 20.


The farnesoid X receptor (FXR) controls the synthesis and transport of bile acids (BAs). Mice lacking expression of FXR, designated Fxr-null, have elevated levels of serum and hepatic BAs and an increase in BA pool size. Surprisingly, at 12 months of age, male and female Fxr-null mice had a high incidence of degenerative hepatic lesions, altered cell foci and liver tumors including hepatocellular adenoma, carcinoma and hepatocholangiocellular carcinoma, the latter of which is rarely observed in mice. At 3 months, Fxr-null mice had increased expression of the proinflammatory cytokine IL-1beta mRNA and elevated beta-catenin and its target gene c-myc. They also had increased cell proliferation as revealed by increased PCNA mRNA and BrdU incorporation. These studies reveal a potential role for FXR and BAs in hepatocarcinogenesis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenoma, Liver Cell / genetics*
  • Animals
  • Bile Acids and Salts / metabolism*
  • Biological Transport
  • Carcinoma, Hepatocellular / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cholangiocarcinoma / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Female
  • Gene Expression
  • Inflammation / genetics
  • Interleukin-1beta / analysis
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • beta Catenin / genetics


  • Bile Acids and Salts
  • DNA-Binding Proteins
  • Interleukin-1beta
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • beta Catenin
  • farnesoid X-activated receptor