Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene

Abstract

The emergence of drug-resistant cancer cells is a major obstacle to cancer treatment. Resistant cells often display a multidrug-resistant phenotype that reduces the promise of combination chemotherapy, the classic approach to the prevention of drug resistance. mdr1, a member of the ABC cassette superfamily of transporters which encodes an energy-dependent drug efflux pump, is the only gene known to confer the multidrug-resistant phenotype. Other multidrug resistance mechanisms must exist, since cell lines which have this phenotype in the absence of mdr1 overexpression have been described. We report here the application of a novel approach involving expression complementary DNA library transfer to the identification of drug-resistant genes. Using this approach we establish that mrp, a member of the ABC cassette superfamily of transporters, is capable of conferring a multidrug-resistant phenotype. This approach should be useful in the identification of other novel resistance genes.