Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance

Molecular Pharmacology
Jean-Philippe AnnereauMichael M Gottesman

Abstract

Discovery of the multidrug resistance protein 1 (MDR1), an ATP-binding cassette (ABC) transporter able to transport many anticancer drugs, was a clinically relevant breakthrough in multidrug resistance research. Although the overexpression of ABC transporters such as P-glycoprotein/ABCB1, MRP1/ABCC1, and MXR/ABCG2 seems to be a major cause of failure in the treatment of cancer, acquired resistance to multiple anticancer drugs may also be multifactorial, involving alteration of detoxification processes, apoptosis, DNA repair, drug uptake, and overexpression of other ABC transporters. As a tool for the study of such phenomena, we designed and created a microarray platform, the ABC-ToxChip, to evaluate relative levels of transcriptional activation among genes involved in the various mechanisms of resistance. In the ABC-ToxChip, a comprehensive set of genes important in toxicological responses (represented by 2200 cDNA probes) is complemented with probes specifically matching ABC transporters as well as oligonucleotides representing 18,000 unique human genes. By comparing the transcriptional profiles of KB-3-1 and DU-145 parental cells with resistant derivatives selected in colchicine (KB-8-5), and 9-nitro-camptothecin (RCO.1), res...Continue Reading

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