DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function.

Vilgelm A, Wei JX, Piazuelo MB, Washington MK, Prassolov V, El-Rifai W, Zaika A
Oncogene. 2008 27 (15): 2170-6

PMID: 17952118 · PMCID: PMC4066670 · DOI:10.1038/sj.onc.1210862

The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. DeltaNp73alpha is an N-terminally truncated isoform of p73. We found that DeltaNp73 protein is upregulated in human gastric carcinoma suggesting that DeltaNp73 may play an oncogenic role in these tumors. Although it has been shown that DeltaNp73alpha 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 DeltaNp73alpha 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 DeltaNp73alpha is mediated by interaction with p53 at the MDR1 promoter.

MeSH Terms (16)

ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 Carcinoma DNA-Binding Proteins Down-Regulation Gene Expression Regulation, Neoplastic Genes, p53 Humans Nuclear Proteins Promoter Regions, Genetic Protein Binding RNA, Messenger Stomach Neoplasms Tumor Cells, Cultured Tumor Suppressor Protein p53 Tumor Suppressor Proteins

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