A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway.

S100A9 (S100 calcium-binding protein A9) is a calcium-binding protein of the S100 family, and its differential expression has been associated with acute and chronic inflammation and several human cancers. Our previous work showed that S100A9 was severely down-regulated in human ESCC (oesophageal squamous cell carcinoma). To further investigate the transcriptional regulation of S100A9, we analysed the S100A9 promoter region and found several putative p53BS (p53-binding sites). Luciferase reporter assays showed that constructs carrying the p53BS exhibited enhanced luciferase activity in response to wild-type p53 activation. Further study demonstrated that S100A9 mRNA and protein expression could be positively regulated in a p53-dependent manner and p53 could bind to p53BS on the S100A9 promoter. Overexpression of S100A9 could induce cellular apoptosis, and this was partly p53-dependent. Knockdown of S100A9 impaired the apoptosis induced by p53. Thus we conclude that a gene down-regulated in ESCC, S100A9, is a novel p53 transcriptional target, induces cellular apoptosis in a partly p53-dependent manner and mediates the p53 apoptosis pathway.