p63 and p73 do not contribute to p53-mediated lymphoma suppressor activity in vivo.
p53 is one of the most important tumor suppressor genes in human cancer, but the roles of its homologues p63 and p73 in tumor suppression, alone or in collaboration with p53, remains controversial. Both p63 and p73 can be deregulated after DNA damage, and induce cell cycle arrest and apoptosis, but mice carrying inactive alleles of these genes do not develop spontaneous tumors. Since heterozygous loss of p53 confers strong sensitization to radiation-induced lymphoma development, we investigated the possibility that radiation exposure may reveal previously undetected tumor suppressor properties in p63 or p73, alone or in combination with p53. Animals heterozygous for p63 or p73, as well as both double heterozygous p53/p63 or p53/p73 mice, showed no significant differences in tumor latency, spectrum or frequency after gamma-radiation, compared to their control counterparts. Deletions were found near the p63 locus on chromosome 16 in radiation-induced tumors, but these frequently included the knockout allele. No deletions or LOH involving the p73 gene were detected, and expression of both genes was maintained in the tumors. We conclude that p53 homologues do not contribute to p53 tumor suppressor activity in lymphoma development.
Perez-Losada
Jesus
J
Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
Wu
Di
D
DelRosario
Reyno
R
Balmain
Allan
A
Mao
Jian-Hua
JH
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C000606460:TP73 protein, human; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins