Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma

is among the mostimportant mediators of the tumor suppressor p53.However, there is increasing evidence indicating that p21could favor tumorigenesis in specific cell types. Inparticular, the absence of p21 delays the development ofthymic lymphomas induced either by ataxia-telangiectasiamutated deficiency or by ionizing irradiation. Here, weextend these observations to the context of p53-deficientmice. The absence of p21 results in a significant extensionof the lifespan of p53-null and p53-haploinsufficient mice,and this effect can be attributed exclusively to a decreasein the incidence of spontaneous thymic lymphomas.Specifically, despite the occurrence of a variety of tumortypes in the context of p53 deficiency, the only tumors thatwere significantly impaired by the absence of p21 werethymic lymphomas. Moreover, the absence of p21 alsodelays the incidence of radiation-induced thymic lympho-mas in p53-deficient mice. Interestingly, p21-deficientlymphomas have a higher apoptotic rate than p21-proficient lymphomas, and this could be on the basis ofthe delayed incidence of thymic lymphomas in the absenceof p21. Together, our results indicate that p21 plays anoncogenic role restricted to thymic lymphomas that ismechanistically independent of p53 and associated to alower tumor apoptotic rate.Oncogene (2006)25, 4128–4132.doi:10.1038/sj.onc.1209432;publishedonline6February2006Keywords: p21;p53;apoptosis;cellcycle;lymphomaThecellcycleinhibitorp21