PMID: 9184795May 1, 1997Paper

Multidrug resistance-associated protein: a protein distinct from P-glycoprotein involved in cytotoxic drug expulsion

General Pharmacology
M A BarrandS Y Neo

Abstract

1. Multidrug resistance (MDR) is a phenomenon originally seen in cultured tumor cells that, following selection for resistance to a single anticancer agent, become resistant to a range of chemically diverse anticancer agents. These MDR cells show a decrease in intracellular drug accumulation due to active efflux by transporter proteins. The transporter best characterized is P-glycoprotein (Pgp). This protein has been identified in many cancers and has been the target for agents able to inhibit its action, thereby reversing resistance. 2. More recently, another transporter, multidrug resistance-associated protein (MRP) has been identified in a number of MDR human tumor cell lines that do not apparently express Pgp. The presence of MRP at the cell surface of these cells is associated with alterations in drug accumulation and distribution. 3. The gene-encoding MRP has been cloned and sequenced and shown by transfection studies to be able to confer resistance and changes in drug accumulation in sensitive tumor cells. The profile of anticancer drugs expelled in the presence of MRP is similar, but not identical, to that of Pgp. 4. MRP has been identified in a number of different types of cancers, but it is not yet clear to what exten...Continue Reading

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