Combined loss of p21 super(waf1/cip1) and p27 super(kip1) enhances tumorigenesis in mice

The cell cycle inhibitors p21 super(Waf1/Cip1) and p27 super(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 de...

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Published inLaboratory investigation Vol. 91; no. 11; pp. 1634 - 1642
Main Authors Garcia-Fernandez, Rosa A, Garcia-Palencia, Pilar, Sanchez, Maria A, Gil-Gomez, Gabriel, Sanchez, Belen, Rollan, Eduardo, Martin-Caballero, Juan, Flores, Juana M
Format Journal Article
LanguageEnglish
Published 01.11.2011
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Summary:The cell cycle inhibitors p21 super(Waf1/Cip1) and p27 super(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.
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ISSN:0023-6837
DOI:10.1038/labinvest.2011.133