ΔNp73α regulates MDR1 expression by inhibiting p53 function

A. Vilgelm, J. X. Wei, M. B. Piazuelo, M. K. Washington, V. Prassolov, W. El-Rifai, A. Zaika

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. ΔNp73α is an N-terminally truncated isoform of p73. We found that ΔNp73 protein is upregulated in human gastric carcinoma suggesting that ΔNp73 may play an oncogenic role in these tumors. Although it has been shown that ΔNp73α 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 ΔNp73α 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 ΔNp73α is mediated by interaction with p53 at the MDR1 promoter.

Original languageEnglish (US)
Pages (from-to)2170-2176
Number of pages7
JournalOncogene
Volume27
Issue number15
DOIs
StatePublished - Apr 3 2008
Externally publishedYes

Keywords

  • Gastric tumor
  • p53
  • p73

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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