The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance.

Multidrug resistance (MDR) is a major hindrance to the successful treatment of neoplastic disease. The development of resistance to multiple chemotherapeutic drugs is a complex phenomenon which has been described in both tumor cell lines and human cancers. To date, two mechanisms associated with overexpression of membrane glycoproteins that function as energy-dependent efflux pumps to reduce intracellular drug levels have been identified for MDR. The first described was the product of the MDR1 gene, P-glycoprotein. The second mechanism is mediated by overexpression of the multidrug resistance-associated protein (MRP). While these proteins both belong to the ATP-binding cassette superfamily of transporters, they are only distantly related. Despite this low homology, they mediate resistance to a similar range of chemotherapeutic drugs. While P-glycoprotein has been well described in the literature, much less is known about the recently identified MRP. This review gives an overview of the characteristics of MRP at both the phenotypic and genotypic levels, and discusses its possible relevance in drug-refractory cancer.