title: Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy.
abstract: BACKGROUND
  The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies.
  
  
  RESULTS
  To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy.
  
  
  CONCLUSIONS
  Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.
authors.affiliation: Molecular Oncology Unit, Division of Biomedicine, CIEMAT, Ave, Complutense 22, E-28040 Madrid, Spain. ramon.garcia@ciemat.es
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Escudero
authors.forename: Ana B
authors.initials: AB
authors.lastname: Martínez-Cruz
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Santos
authors.forename: Corina
authors.initials: C
authors.lastname: Lorz
authors.forename: Carmen
authors.initials: C
authors.lastname: Segrelles
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garaulet
authors.forename: Cristina
authors.initials: C
authors.lastname: Saiz-Ladera
authors.forename: Clotilde
authors.initials: C
authors.lastname: Costa
authors.forename: Agueda
authors.initials: A
authors.lastname: Buitrago-Pérez
authors.forename: Marta
authors.initials: M
authors.lastname: Dueñas
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Paramio
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53