Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice
Open accessAbstract
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.
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Ablation of Fxr promotes cholestasis, NAFLD, NASH and HCC in mice.
“Ablation of Nr1h4 (hereafter referred to as Fxr) not only promotes cholestasis but also NAFLD, NASH and HCC in mice (Kim et al., 2007; Lu et al., 2000; Wang et al., 2008; Watanabe et al., 2004; Yang et al., 2007).”
From Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis (2016) · cites this paper as Kim et al., 2007
Fxr-deficient mice have compromised intestinal integrity, further deterioration after bile duct ligation, and a high incidence of HCC.
“Fxr-deficient mice exhibit compromised intestinal integrity, with further deterioration after bile duct ligation20, and a high incidence of HCC140.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [140]
Nr1h4−/− mice develop spontaneous hepatic inflammation and liver tumors.
“Nr1h4−/− mice also develop spontaneous hepatic inflammation and liver tumors (I. Kim et al., 2007; Yang et al., 2007).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as I. Kim et al., 2007
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- Authors
- Kim, I., Morimura, K., Shah, Y., Yang, Q., Ward, J. M., & Gonzalez, F. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gonzalez, Frank J.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-20
- Volume
- 28
- Issue
- 5
- Pages
- 940-946
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- PMC
- PMC1858639
- OpenAlex
- W2166661344
- Cited by
- 357
- References
- 38
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 19 · 2023: 19 · 2022: 24 · 2021: 18 · 2020: 13 · 2019: 12 · 2018: 19 · 2017: 26 · 2016: 20 · 2015: 19 · 2014: 22 · 2013: 21 · 2012: 27
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01BC005708)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- farnesoid X receptor, hepatocarcinogenesis, bile acids, bile acid pool size, liver tumors, hepatocellular carcinoma, hepatocellular adenoma, IL-1β, β-catenin, c-Myc, cell proliferation, PCNA, BrdU incorporation
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Biological Transport, Cell Transformation, Neoplastic, DNA-Binding Proteins, Female, Carcinoma, Hepatocellular, Inflammation, Liver, Liver Neoplasms, Male, Mice, Mutant Strains, Transcription Factors, Gene Expression, Receptors, Cytoplasmic and Nuclear, Adenoma, Liver Cell, Cholangiocarcinoma, Cell Proliferation, beta Catenin, Mice, Interleukin-1beta
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