RGD Reference Report - Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. - Rat Genome Database

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Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice.

Authors: Kim, Insook  Morimura, Keiichirou  Shah, Yatrik  Yang, Qian  Ward, Jerrold M  Gonzalez, Frank J 
Citation: Kim I, etal., Carcinogenesis. 2007 May;28(5):940-6. doi: 10.1093/carcin/bgl249. Epub 2006 Dec 20.
RGD ID: 14696794
Pubmed: PMID:17183066   (View Abstract at PubMed)
PMCID: PMC1858639   (View Article at PubMed Central)
DOI: DOI:10.1093/carcin/bgl249   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NR1H4Humanhepatocellular adenoma  ISONr1h4 (Mus musculus) RGD 
Nr1h4Rathepatocellular adenoma  ISONr1h4 (Mus musculus) RGD 
Nr1h4Mousehepatocellular adenoma  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Mus musculus)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Homo sapiens)
NR1H4  (nuclear receptor subfamily 1 group H member 4)


Additional Information