Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family.
p63 and p73 are functionally and structurally related to the tumor suppressor p53. However, their own role in tumor suppression is unclear. Given the p53-like properties of p63 and p73, we tested whether they are involved in tumor suppression by aging mice heterozygous for mutations in all p53 family genes and scored for spontaneous tumors. We show here that p63+/-;p73+/- mice develop spontaneous tumors. Loss of p63 and p73 can also cooperate with loss of p53 in tumor development. Mice heterozygous for mutations in both p53 and p63 or p53 and p73 displayed higher tumor burden and metastasis compared to p53+/- mice. These findings provide evidence for a broader role for the p53 family than has been previously reported.
Flores
Elsa R
ER
The University of Texas M.D. Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences, Department of Molecular and Cellular Oncology, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Sengupta
Shomit
S
Miller
John B
JB
Newman
Jamie J
JJ
Bronson
Roderick
R
Crowley
Denise
D
Yang
Annie
A
McKeon
Frank
F
Jacks
Tyler
T
D000230:Adenocarcinoma / Q000235:genetics; D019588:Aging, Premature / Q000235:genetics; D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D008136:Longevity / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D015674:Mammary Neoplasms, Animal / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins