ΔNp73α regulates MDR1 expression by inhibiting p53 function
| Autor: | Vladimir S. Prassolov, Alexander Zaika, Jinxiong Wei, Anna E. Vilgelm, Wael El-Rifai, Mary Kay Washington, Maria Blanca Piazuelo |
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| Rok vydání: | 2007 |
| Předmět: |
Gene isoform
Cancer Research ATP Binding Cassette Transporter Subfamily B Tumor suppressor gene Down-Regulation Plasma protein binding Biology medicine.disease_cause Article Downregulation and upregulation Stomach Neoplasms Tumor Cells Cultured Genetics medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger Nuclear protein Promoter Regions Genetic neoplasms Molecular Biology Transcription factor Tumor Suppressor Proteins Carcinoma Nuclear Proteins Genes p53 DNA-Binding Proteins Gene Expression Regulation Neoplastic Cancer cell Cancer research Tumor Suppressor Protein p53 Carcinogenesis Protein Binding |
| Zdroj: | Oncogene. 27:2170-2176 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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