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Cell Growth & Differentiation Vol. 12, 223-231, May 2001
© 2001 American Association for Cancer Research

Hepatoblast-like Cells Populate the Adult p53 Knockout Mouse Liver

Evidence for a Hyperproliferative Maturation-arrested Stem Cell Compartment1

Melissa L. Dumble, Belinda Knight, Elizabeth A. Quail and George C. T. Yeoh2

Department of Biochemistry, The University of Western Australia, Crawley 6009, Western Australia, Australia

Although p53 regulates the cell cycle and apoptosis, gross embryonic development is normal in the p53 knockout (-/-) mouse. In this study, we comprehensively assessed liver development in p53 -/- mice (from embryonic day 15 to adult) for evidence of a cell cycle-induced perturbation in differentiation. Liver cell proliferation in the embryo and newborn is similar in p53 -/- and +/+ mice; in contrast, -/- adult hepatocytes divide at twice the rate of wild types. Developmental expression patterns of liver-specific markers that are up-regulated (e.g., phosphoenolpyruvate carboxykinase and aldolase B) and down-regulated (e.g., {alpha}-fetoprotein) are similar. Therefore, embryonic and perinatal liver development is normal in the absence of p53. However, the p53 -/- adult liver displays small blast-like cells, the majority being hepatic and some lymphoid. These cells appear in periportal regions and can infiltrate the parenchyma. The hepatic blast-like cells express both mature and immature liver markers, suggesting that differentiation of the liver stem cell compartment is blocked.




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Cancer Research Clinical Cancer Research
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Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.