Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene.
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.
Kruh
G D
GD
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Chan
A
A
Myers
K
K
Gaughan
K
K
Miki
T
T
Aaronson
S A
SA
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004317:Doxorubicin / Q000633:toxicity*; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D051379:Mice; D014162:Transfection; D014407:Tumor Cells, Cultured
D004317:Doxorubicin