%0 Journal Article %A ANA BELÉN MARTÍNEZ-CRUZ %A MIRENTXU SANTOS %A RAMÓN GARCÍA-ESCUDERO %A MARTA MORAL %A CARMEN SEGRELLES %A CORINA LORZ %A CRISTINA SAIZ %A ÁGUEDA BUITRAGO-PÉREZ %A CLOTILDE COSTA %A JESÚS M. PARAMIO %T Spontaneous Tumor Formation in Trp53-deficient Epidermis Mediated by Chromosomal Instability and Inflammation %D 2009 %J Anticancer Research %P 3035-3042 %V 29 %N 8 %X Background: The specific ablation of Trp53 gene in mouse epidermis leads to the spontaneous development of aggressive squamous cell carcinoma, a process that is accelerated by the subsequent loss of Rb gene. Materials and Methods: The possible mechanisms leading to spontaneous tumor formation in epidermis in the absence of Trp53 were studied focusing on hair cycle defects, inflammation and possible chromosomal instability (CIN). Results: Loss of p53 induces tumorigenesis primarily by mediating early CIN and, to a minor extent, nuclear factor κB activation. Notably, CIN occurs not only in p53-deficient skin, but also in epidermis lacking both Rb and Tp53 tumor suppressors, indicating a predominant role of this process in spontaneous tumorigenesis. Conclusion: These data identify CIN as a major mechanism in tumorigenesis originated by Trp53 loss in stratified epithelia and imply that therapies aimed to counterbalance CIN might be of relevance for the treatment of human cancer bearing impaired p53 functions. %U https://ar.iiarjournals.org/content/anticanres/29/8/3035.full.pdf