Journal
LABORATORY INVESTIGATION
Volume 91, Issue 11, Pages 1634-1642Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2011.133
Keywords
animal model; cyclin-dependent kinase inhibitor; p27(Kip1); p21(Waf1/Cip1); tumor development
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Funding
- Santander Bank
- UCM University [GR 58/08]
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The cell cycle inhibitors p21(Waf1/Cip1) and p27(Kip1) are frequently downregulated in many human cancers, and correlate with a worse prognosis. We show here that combined deficiency in p21 and p27 proteins in mice is linked to more aggressive spontaneous tumorigenesis, resulting in a decreased lifespan. The most common tumors developed in p21p27 double-null mice were endocrine, with a higher incidence of pituitary adenomas, pheochromocytomas and thyroid adenomas. The combined absence of p21 and p27 proteins delays the incidence of radiation-induced thymic lymphomas with a higher apoptotic rate, measured by active caspase-3 and cleaved PARP-1 immunoexpresion. These results provide experimental evidence for a cooperation of both cyclin-dependent kinase inhibitors in tumorigenesis in mice. Laboratory Investigation (2011) 91, 1634-1642; doi:10.1038/labinvest.2011.133; published online 29 August 2011
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