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Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice.

ABSTRACT: 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.

SUBMITTER: Kim I

PROVIDER: S-EPMC1858639 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice.

Kim Insook I Morimura Keiichirou K Shah Yatrik Y Yang Qian Q Ward Jerrold M JM Gonzalez Frank J FJ

Carcinogenesis 20061220 5

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 ...[more]

PMID: 17183066

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| S-EPMC5319891 | biostudies-other

Increased activation of the Wnt/?-catenin pathway in spontaneous hepatocellular carcinoma observed in farnesoid X receptor knockout mice.

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Project description:Expression profiling of whole body (WB) FXR knockout (KO) mice (FXR WB KO), liver-specific FXR KO mice (AFXR Cre+) and enterocyte specific FXR KO mice (VFXR Cre+) on a C57BL/6J genetic background Whole body (WB) FXR knockout (KO) mice (FXR WB KO), liver-specific FXR KO mice (AFXR Cre+) and enterocyte specific FXR KO mice (VFXR Cre+) on a C57BL/6J genetic background were bred and maintained in the laboratory animal research facility at the University of Kansas Medical Center in rooms under a 12-hour light-dark cycle. All experiments used 10-16 week-old male mice. FXR was activated by treatment with the FXR synthetic agonist, GW4064, at 150 mg/kg. GW4064 or vehicle was administered by oral gavage at 6 p.m., followed by a second administration at 8 a.m. the next morning. Two hours later, the liver was harvested.

2014-01-31 | E-GEOD-54557 | biostudies-arrayexpress

Impaired Intestinal Farnesoid X Receptor Signaling in Cystic Fibrosis Mice.

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| S-EPMC6881665 | biostudies-literature

Transcription profiling of liver from farnesoid X receptor knockout mice

2014-01-31 | GSE54557 | GEO

Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice.

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Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice.

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| S-EPMC3343176 | biostudies-literature

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