The oncogenic roles of p53 mutants in mouse models.
Tumors associated with p53 usually contain missense mutations in the p53 tumor suppressor gene rather than deletions of p53, suggesting a growth advantage for cells with missense mutations. The oncogenic roles of p53 mutants have been examined extensively in cell lines. Mouse models that inherit p53 mutations expressed at physiological levels have now been generated to examine the activities of mutant p53 upon tumorigenesis in vivo. Mice with p53 mutations develop tumor spectrums and metastatic phenotypes different from those of mice with a p53-null allele. Embryo fibroblasts with mutant p53 also show increased proliferative and transformation properties. One mechanism for this gain-of-function potential is the inhibition of function of the p53 family members p63 and p73.
Lozano
Guillermina
G
Department of Cancer Genetics, Box 1010, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. gglozano@mdanderson.org
D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins; D009857:Oncogenes / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins; D015534:Trans-Activators; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins