Protective role of p53 in skin cancer: Carcinogenesis studies in mice lacking epidermal p53
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Angustias Page1,2, Manuel Navarro1,2, Cristian Suarez-Cabrera1,2, Josefa P. Alameda1,2, M. Llanos Casanova1,2, Jesús M. Paramio1,2, Ana Bravo3, Angel Ramirez1,2
1Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
2Biomedical Research Institute I+12, University Hospital “12 de Octubre”, Madrid, Spain
3Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Santiago de Compostela, Lugo, Spain
Angel Ramirez, e-mail: [email protected]
Keywords: p53, transgenic mice, papilloma, skin SCC, DMBA/TPA
Received: November 28, 2015 Accepted: February 18, 2016 Published: March 3, 2016
p53 is a protein that causes cell cycle arrest, apoptosis or senescence, being crucial in the process of tumor suppression in several cell types. Different in vitro and animal models have been designed for the study of p53 role in skin cancer. These models have revealed opposing results, as in some experimental settings it appears that p53 protects against skin cancer, but in others, the opposite conclusion emerges. We have generated cohorts of mice with efficient p53 deletion restricted to stratified epithelia and control littermates expressing wild type p53 and studied their sensitivity to both chemically-induced and spontaneous tumoral transformation, as well as the tumor types originated in each experimental group. Our results indicate that the absence of p53 in stratified epithelia leads to the appearance, in two-stage skin carcinogenesis experiments, of a higher number of tumors that grow faster and become malignant more frequently than tumors arisen in mice with wild type p53 genotype. In addition, the histological diversity of the tumor type is greater in mice with epidermal p53 loss, indicating the tumor suppressive role of p53 in different epidermal cell types. Aging mice with p53 inactivation in stratified epithelia developed spontaneous carcinomas in skin and other epithelia. Overall, these results highlight the truly protective nature of p53 functions in the development of cancer in skin and in other stratified epithelia.
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