title: Control of genomic instability and epithelial tumor development by the p53-Fbxw7/Cdc4 pathway.
abstract: Mouse models of cancer have provided novel insights into the timing of p53 loss during tumorigenesis. We have recently identified Fbxw7/Cdc4 as a downstream target of p53 loss that controls genomic instability and tumor development in epithelial tumors. Although p53-deficient mice primarily develop lymphomas and sarcomas, the additional loss of one copy of the Fbxw7 gene drives tumor development in a range of epithelial tissues. These data highlight the importance of genetic instability at the chromosome level in the development of common cancer types, and further illustrate the value of mouse models in identifying causal genetic events in epithelial tumor formation.
authors.affiliation: Cancer Research Institute, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Losada
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D004249:DNA Damage; D004195:Disease Models, Animal; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005354:Fibrosarcoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C513272:Fbxw7 protein, mouse; D044767:Ubiquitin-Protein Ligases