Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor

Fan Yang, Xiongfei Huang, Tangsheng Yi, Yun Yen, David D. Moore, Wendong Huang

Research output: Contribution to journalArticle

285 Citations (Scopus)

Abstract

Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, lipid, and glucose homeostasis. Both male and female FXR mice spontaneously developed liver tumors; however, no other tumors were developed after 15 months of age. In contrast, no liver tumors were observed in wild-type mice of the same age. Histologie analyses confirm that tumors were hepatocellular adenoma and carcinoma. Although there was no obvious tumor at ages 9 to 12 months, FXR -/- livers displayed prominent liver injury and inflammation. Strong labeling of apoptotic hepatocytes and liver damage-induced compensatory regeneration were observed. Deregulation of genes involved in bile acid homeostasis in FXR-/- mice was consistent with abnormal levels of bile acids presented in serum and liver. Genes involved in inflammation and cell cycle were up-regulated in aging FXR-/- mice but not in wild-type controls. Increasing the bile acid levels by feeding mice with a 0.2% cholic acid diet strongly promoted N-nitrosodiethylamine-initiated liver tumorigenesis, whereas lowering bile acid pool in FXR mice by a 2% cholestyramine feeding significantly reduced the malignant lesions. Our results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis.

Original languageEnglish
Pages (from-to)863-867
Number of pages5
JournalCancer Research
Volume67
Issue number3
DOIs
Publication statusPublished - Feb 1 2007
Externally publishedYes

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Bile Acids and Salts
Liver
Neoplasms
Homeostasis
Liver Cell Adenoma
Inflammation
Cholestyramine Resin
Cholic Acid
Diethylnitrosamine
Cytoplasmic and Nuclear Receptors
Genes
Regeneration
Hepatocytes
Hepatocellular Carcinoma
Cell Cycle
Carcinogenesis
Diet
Lipids
Glucose
Wounds and Injuries

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. / Yang, Fan; Huang, Xiongfei; Yi, Tangsheng; Yen, Yun; Moore, David D.; Huang, Wendong.

In: Cancer Research, Vol. 67, No. 3, 01.02.2007, p. 863-867.

Research output: Contribution to journalArticle

Yang, Fan ; Huang, Xiongfei ; Yi, Tangsheng ; Yen, Yun ; Moore, David D. ; Huang, Wendong. / Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. In: Cancer Research. 2007 ; Vol. 67, No. 3. pp. 863-867.
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