Abstract
Induction of apoptosis by the tumor suppressor p53 is known to protect from Mycβdriven lymphomagenesis. The p53 family member p73 is also a proapoptotic protein, which is activated in response to oncogenes like Myc. Here, we have investigated whether p73 provides a similar protection from Mycβdriven lymphomas as p53. Confirming previous studies, the inactivation of a single p53 allele (p53^+/β^) strongly reduced the median survival of EΞΌβMyc transgenic mice from 103 to 39 days and was invariably associated with a loss of the wildβtype p53 allele. In contrast, mutational inactivation of a p73 allele (p73^+/β^) reduced the median survival by only 12 days. Lymphomas that developed in the p73^+/β^ background showed no loss of heterozygosity (LOH). Furthermore, gene expression profiling of p73^+/+^, p73^+/β^ and p73^β/β^ lymphomas indicated that p73^+/β^ lymphomas retained p73 transcriptional activity. Subtle gene expression differences between p73^+/+^ and p73^+/β^ lymphomas, however, suggest a haploinsufficient phenotype on some p73 target genes. This might help to explain why p73^+/β^ animals succumbed to disease slightly earlier than their p73^+/+^ littermates (logβrank test p < 0.0395) and why p73 often shows monoallelic inactivation in human lymphomas. Together these data demonstrate that in Mycβdriven lymphomagenesis p73 has weak tumor suppressor activity compared with p53. Β© 2008 WileyβLiss, Inc.