1. ¹Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
2. ²Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA
3. ³Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA
4. ⁴Department of Cell Biology, Engelhardt Institute of Molecular Biology, Russian Acad. Sci., Moscow, Russia
5. ⁵Department of Cancer Biology, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

Correspondence: Professor A Zaika, Department of Surgery and Cancer Biology, Vanderbilt University Medical Center, 1255 Light Hall, 2215 Garland Ave., Nashville, TN 37232, USA. E-mail: alex.zaika@vanderbilt.edu

Received 16 March 2007; Revised 20 August 2007; Accepted 10 September 2007; Published online 22 October 2007.

Abstract

The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. Np73 is an N-terminally truncated isoform of p73. We found that Np73 protein is upregulated in human gastric carcinoma suggesting that Np73 may play an oncogenic role in these tumors. Although it has been shown that Np73 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 Np73 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 Np73 is mediated by interaction with p53 at the MDR1 promoter.