title: Spontaneous tumor formation in Trp53-deficient epidermis mediated by chromosomal instability and inflammation.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Molecular Oncology Unit, Division of Biomedicine, CIEMAT, Ave. Complutense 22, E-28040 Madrid, Spain.
authors: Ana Belén
authors: AB
authors: Martínez-Cruz
authors: Mirentxu
authors: M
authors: Santos
authors: Ramón
authors: R
authors: García-Escudero
authors: Marta
authors: M
authors: Moral
authors: Carmen
authors: C
authors: Segrelles
authors: Corina
authors: C
authors: Lorz
authors: Cristina
authors: C
authors: Saiz
authors: Agueda
authors: A
authors: Buitrago-Pérez
authors: Clotilde
authors: C
authors: Costa
authors: Jesús M
authors: JM
authors: Paramio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology*; D043171:Chromosomal Instability; D020869:Gene Expression Profiling; D007249:Inflammation; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D016160:Retinoblastoma Protein / Q000502:physiology; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C045073:Cre recombinase; D019426:Integrases