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 kappaB 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.
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 kappaB activation. Notably, CIN occurs not only in p53-deficient skin, but also in epidermis lacking both Rb and Tp53tumor 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 humancancer bearing impaired p53 functions.
Authors: Corina Lorz; Ramón García-Escudero; Carmen Segrelles; Marina I Garín; José M Ariza; Mirentxu Santos; Sergio Ruiz; María F Lara; Ana B Martínez-Cruz; Clotilde Costa; Agueda Buitrago-Pérez; Cristina Saiz-Ladera; Marta Dueñas; Jesús M Paramio Journal: Stem Cell Rev Rep Date: 2010-06 Impact factor: 5.739
Authors: Clotilde Costa; Mirentxu Santos; Carmen Segrelles; Marta Dueñas; M Fernanda Lara; Xabier Agirre; Felipe Prosper; Ramón García-Escudero; Jesús M Paramio Journal: Sci Rep Date: 2012-11-09 Impact factor: 4.379
Authors: Olga Bornachea; Mirentxu Santos; Ana Belén Martínez-Cruz; Ramón García-Escudero; Marta Dueñas; Clotilde Costa; Carmen Segrelles; Corina Lorz; Agueda Buitrago; Cristina Saiz-Ladera; Xabier Agirre; Teresa Grande; Beatriz Paradela; Antonio Maraver; José M Ariza; Felipe Prosper; Manuel Serrano; Montse Sánchez-Céspedes; Jesús M Paramio Journal: Sci Rep Date: 2012-05-31 Impact factor: 4.379
Authors: Angustias Page; Manuel Navarro; Cristian Suarez-Cabrera; Josefa P Alameda; M Llanos Casanova; Jesús M Paramio; Ana Bravo; Angel Ramirez Journal: Oncotarget Date: 2016-04-12