Microarray-based detection of multidrug resistance in human tumor cells by expression profiling of ATP-binding cassette transporter genes

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 24; pp. 8987 - 8993
• Main Authors: GILLET, Jean-Pierre, EFFERTH, Thomas, STEINBACH, Daniel, HAMELS, Jacques, DE LONGUEVILLE, Francoise, BERTHOLET, Vincent, REMACLE, José
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-12-2004
• Subjects: Antineoplastic agents; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cell Line, Tumor; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - genetics; Gene Expression Profiling; HL-60 Cells; Humans; Leukemia, T-Cell - drug therapy; Leukemia, T-Cell - genetics; Medical sciences; Oligonucleotide Array Sequence Analysis - methods; Pharmacology. Drug treatments; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Antineoplastic agent; Human; Treatment resistance; Gene; Multiple resistance; DNA chip; Genetics; Diagnosis; Detection; ABC transporter; Tumor cell; Gene expression profile
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-04-1978

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.