LOCALIZATION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN, MRP, IN RESISTANT LARGE-CELL LUNG-TUMOR CELLS

The drug transport protein, P-glycoprotein, confers multidrug resistan ce (MDR) by expelling drugs across the cell surface. The structurally similar multidrug resistance-associated protein, or MRP, is also invol ved with drug efflux. In MDR variants of the human lung tumour cell li ne COR-L23 that overexpress MRP, there are also changes in intracellul ar drug distribution. To ascertain whether MRP could be involved in ei ther process, experiments were performed to identify where MRP was loc ated in these cells. Following separation of membranes by sucrose grad ient centrifugation, MRP was found predominantly in the lighter membra ne fractions containing plasma membrane enzyme activity. Immunofluores cent staining with a monoclonal antibody raised against MRP confirmed that MRP is present at the cell surface of these MDR lung tumour cells .