Absence of p53-dependent induction of the metastatic suppressor KAI1 gene after DNA damage

The p53 tumor suppressor protein functions to monitor the integrity of the genome. If a damage is detected, p53 binds tightly to specific sequence ele ments in the DNA and induces the transactivation of genes involved in vario us growth regulatory processes such as cell cycle progression, DNA repair a nd apoptosis, A p53-binding site was recently identified in the promoter re gion of the metastatic suppressor KAI1 gene, suggesting that this gene was a direct transcriptional target of p53. To test the relevance of this hypot hesis, we studied the endogenous KAI1 expression in a series of human cell lines with varying p53 status in response to genotoxic treatment as well as in different cellular models exhibiting an inducible p53 activity. Overall , our data indicate that KAI1 expression is not significantly modulated by p53. This observation provides a direct evidence that the presence of a p53 -binding site in regulatory domains is not a sufficient criteria to define a p53-transcriptional target gene.