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[Cancer Research 64, 8987-8993, December 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Microarray-based Detection of Multidrug Resistance in Human Tumor Cells by Expression Profiling of ATP-binding Cassette Transporter Genes

Jean-Pierre Gillet1, Thomas Efferth2, Daniel Steinbach3, Jacques Hamels4, Françoise de Longueville5, Vincent Bertholet5 and José Remacle1

1 Research Unit of Cellular Biology, University of Namur, Namur, Belgium; 2 Center for Molecular Biology of the University of Heidelberg, Heidelberg, Germany; 3 University Children’s Hospital Jena, Department of Pediatrics, Jena, Germany; 4 Genetic and Pathology Institute, Department of Pathology and Molecular Onco-Hematology, Loverval, Belgium; and 5 Eppendorf Array Technologies, Namur, Belgium

Different mechanisms of drug resistance, including ATP-binding cassette (ABC) transporters, are responsible for treatment failure of tumors. We developed a low-density DNA microarray which contains 38 genes of the ABC transporter gene family. This tool has been validated with three different multidrug-resistant sublines (CEM/ADR5000, HL60/AR, and MCF7/CH1000) known to overexpress either the ABCB1 (MDR1), ABCC1 (MRP1), or ABCG2 (MXR and BCRP) genes. When compared with their drug-sensitive parental lines, we observed not only the overexpression of these genes in the multidrug-resistant cell lines but also of other ABC transporter genes pointing to their possible role in multidrug resistance. These results were corroborated by quantitative real-time reverse transcription-PCR. As the microarray allows the determination of the expression profile of many ABC transporters in a single hybridization experiment, it may be useful as a diagnostic tool to detect drug resistance in clinical samples.




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