The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
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 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
In the citing paper
“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]
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“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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Citations
Cites
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00062-3 · Cited by 1,819
Self-citationKraupp, B. G., Ruttkay-Nedecký, B., Koudelka, H., Bukowska, K., Bursch, W., & Schulte‐Hermann, R. (1995) · Hepatology · doi:10.1002/hep.1840210534 · Cited by 1,223
Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice
Zhang, Y., Lee, F. Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506982103 · Cited by 974
Self-citationNuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration
Huang, W., Ma, K., Zhang, J., Qatanani, M., Cuvillier, J., Liu, J., Dong, B., Huang, X., & Moore, D. D. (2006) · Science · doi:10.1126/science.1121435 · Cited by 645
Endocrine functions of bile acids
Houten, S. M., 渡辺, 光., & Auwerx, J. H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601049 · Cited by 595
The Farnesoid X Receptor Modulates Adiposity and Peripheral Insulin Sensitivity in Mice
Cariou, B., van Harmelen, K., Durán-Sandoval, D., van Dijk, T. H., Grefhorst, A., Abdelkarim, M., Caron, S., Torpier, G., Fruchart, J., Gonzalez, F. J., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510258200 · Cited by 546
Self-citationToxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas
Faubion, W. A., Guicciardi, M. E., Miyoshi, H., Bronk, S. F., Roberts, P. J., Svingen, P. A., Kaufmann, S. H., & Gores, G. J. (1999) · Journal of Clinical Investigation · doi:10.1172/jci4765 · Cited by 539
Fiorucci, S., Antonelli, E., Rizzo, G., Renga, B., Mencarelli, A., Riccardi, L., Orlandi, S., Pellicciari, R., & Morelli, A. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.001 · Cited by 472
Activation of hepatic stellate cells - a key issue in liver fibrosis
Reeves, H. L. (2002) · Frontiers in bioscience · doi:10.2741/reeves · Cited by 421
Peraino, C., Fry, R. J., & Staffeldt, E. F. (1971) · PubMed · Cited by 410
Research works printed but not linked: 1
- Haseman, 1999, Chapter 26, Neoplasm Incidences in B6C3F1 Mice: NTP Historical Data
Cited by
Sorted by citations
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876
“Nr1h4 / mice also develop spontaneous hepatic inflammation and liver tumors (Kim et al., 2007; Yang et al., 2007).”
BackgroundBile acid receptors as targets for drug development
Schaap, F. G., Trauner, M., & Jansen, P. L. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.151 · Cited by 696
The gut microbiome and liver cancer: mechanisms and clinical translation
Yu, L.-X., & Schwabe, R. F. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.72 · Cited by 634
Metadata
- 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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