The p53 gene and its homologue p73 are rarely mutated in neuroblastoma. In 
recent studies, we showed that overexpression of DeltaNp73alpha, an isoform 
lacking the N-terminal transactivation (TA) domain, surprisingly induces p53 
protein accumulation in the wild-type (wt) p53 human neuroblastoma line SH-SY5Y. 
As can be expected owing to its dominant-negative effect, DeltaNp73alpha 
inhibits Waf1/p21 gene expression, but equally importantly, it upregulates 
BTG2TIS21/PC3, another p53 target gene. This effect is not observed in 
neuroblastoma cells that express a mutated p53. To better understand the 
DeltaNp73-mediated transactivation of the BTG2TIS21/PC3 gene we performed 
luciferase assays with two reporter plasmids harboring long and short BTG2 
promoter sequences in three human neuroblastoma cell lines and one breast cancer 
cell line. Our results demonstrate that BTG2TIS21/PC3 transactivation by 
DeltaNp73alpha depends on both p53 status (as it is not observed in a p53-/- 
neuroblastoma cell line) and cellular context (as it occurs in a p53+/+ 
neuroblastoma cell line but not in a p53+/+ breast tumor cell line). The fact 
that DeltaNp73alpha may either inhibit or stimulate wt-p53 transcriptional 
activity, depending on both the p53 target gene and the cellular context, was 
confirmed by real-time quantitative PCR. Moreover, transactivation of the 
BTG2TIS21/PC3 promoter requires a complete DeltaNp73alpha C-terminus sequence as 
it is not observed with DeltaNp73beta, which lacks most of the C-terminal 
domain. We have previously shown that DeltaNp73alpha is the only p73 isoform 
expressed in undifferentiated neuroblastoma tumors. In light of all these 
findings, we propose that DeltaNp73alpha not only acts as an inhibitor of 
p53/TAp73 functions in neuroblastoma tumors, but also cooperates with wt-p53 in 
playing a physiological role through the activation of BTG2TIS21/PC3 gene 
expression.