ΔNp73α regulates MDR1 expression by inhibiting p53 function

The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. Delta Np73 alpha is an N-terminally truncated isoform of p73. We found that Delta Np73 protein is upregulated in human gastric carcinoma suggesting that DNp73 may play an oncogenic role in these tumors. Although it has been shown that DNp73a inhibits apoptosis and counteracts the effect of chemotherapeutic drugs, the underlying mechanism by which this p73 isoform contributes to chemotherapeutic drug response remains to be explored. We found that DNp73a upregulates MDR1 mRNA and p-glycoprotein (p-gp), which is involved in chemotherapeutic drug transport. This p-gp upregulation was accompanied by increased p-gp functional activity in gastric cancer cells. Our data suggest that upregulation of MDR1 by DNp73a is mediated by interaction with p53 at the MDR1 promoter.