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

• Published in: Cancer research (Chicago, Ill.) Vol. 54; no. 7; pp. 1649 - 1652
• Main Authors: KRUH, G. D, CHAN, A, MYERS, K, GAUGHAN, K, MIKI, T, AARONSON, S. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-04-1994
• Subjects: 3T3 Cells; Animals; Antineoplastic agents; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Clone Cells; Doxorubicin - toxicity; Drug Resistance - genetics; Gene Expression; Gene Library; General aspects; Humans; Leukemia, Promyelocytic, Acute; Medical sciences; Mice; Pharmacology. Drug treatments; Transfection; Tumor Cells, Cultured; Antineoplastic agent; Complementary DNA; Multiple resistance; 3T3-Cell line; Anthracyclins; In vitro; Mechanism; Genetic transfer
• ISSN: 0008-5472; 1538-7445

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.