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- Molecular carcinogenesis
- mucosal immunity
- gut immunology
- colorectal adenomas
- colon carcinogenesis
- premalignancy - GI tract
- colorectal neoplasia
- colonic polyps
β-catenin and hepatocyte regeneration—a role in hepatocellular carcinoma?
▶ Wang EY, Yeh SH, Tsai TF, et al. Depletion of β-catenin from mature hepatocytes of mice promotes expansion of hepatic progenitor cells and tumor development. Proc Natl Acad Sci U S A 2011;108:18384–9.
Mature hepatocytes turn over relatively slowly. The long-term effects of hepatocyte β-catenin deficiency have not been fully addressed. Previous conditional β-catenin knockout (KO) mice studies demonstrated only modest reduction in liver mass. Wang and colleagues followed conditional KO mice (Alb-Cre;Ctnnb1flx/flx) until 20 months of age. Selective depletion of β-catenin in hepatocytes was confirmed in mice at 2 months of age. Surprisingly, after 7 months of age the mice began to recover β-catenin in liver, and by 18 months the levels were near those of wild-type mice. Immunohistochemical staining of liver tissue revealed clusters of β-catenin-expressing cells that also expressed progenitor cell markers such as CK19. During follow-up, the KO mice spontaneously developed β-catenin positive liver tumours that stained strongly for CK19. When Alb-Cre;Ctnnb1flx/flx mice were crossed with transgenic mice harbouring the hepatitis B virus HBx gene, hepatic repopulation with β-catenin-expressing cells was more rapid as was the rate of tumour development. Hepatocyte regeneration is the main source of new cells in normal liver. However, progenitor cells appear to contribute to the hepatocyte population in chronic liver diseases. These data suggest that hepatocellular carcinoma may arise from hepatic progenitor cells in liver where hepatocyte regenerative capacity is impaired. The tumour-prone nature of hepatic progenitor cells is supported by the co-carcinogenicity of HBx in the current study. Wang and colleagues suggest that β-catenin KO mice would be an appropriate model to investigate the role of progenitor cells in the genesis of hepatocellular carcinoma.
Immune regulation in the pathogenesis of hepatocellular carcinoma
▶ Kang TW, Yevsa T, Woller N, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011;479:547–51.
Hepatocellular carcinoma (HCC) …
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