Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
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ABSTRACT:
SUBMITTER: Willenbring H
PROVIDER: S-EPMC2526059 | biostudies-literature | 2008 Jul
REPOSITORIES: biostudies-literature
Publications
Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
Willenbring Holger H Sharma Amar Deep AD Vogel Arndt A Lee Andrew Y AY Rothfuss Andreas A Wang Zhongya Z Finegold Milton M Grompe Markus M
Cancer cell 20080701 1
Accumulation of toxic metabolites in hereditary tyrosinemia type I (HT1) patients leads to chronic DNA damage and the highest risk for hepatocellular carcinomas (HCCs) of any human disease. Here we show that hepatocytes of HT1 mice exhibit a profound cell-cycle arrest that, despite concomitant apoptosis resistance, causes mortality from impaired liver regeneration. However, additional loss of p21 in HT1 mice restores the proliferative capabilities of hepatocytes and renal proximal tubular cells. ...[more]
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