ANALYSIS OF THE EXPRESSION OF MRP, THE GENE FOR A NEW PUTATIVE TRANSMEMBRANE DRUG TRANSPORTER, IN HUMAN MULTIDRUG RESISTANT LUNG-CANCER CELL-LINES

Human cells can become multidrug resistant (MDR) by an increase in the activity of the MDR1 P-glycoprotein or by other, as vet unknown mecha nisms, referred to as non-P-glycoprotein mediated MDR (non-Pgp MDR). S . P. C. Cole et al. [Science (Washington DC), 258: 1650-1654, 1992] re cently reported that in two cell lines non-Pgp MDR was associated with the overexpression of a new putative membrane transporter gene, MRP. Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW-1573 ( non-small cell lung cancer) and GLC4 (small cell lung cancer). In all of ten SW-1573 derived lines examined the MRP mRNA level was equal to that in the parental line, whereas MRP was 25-fold overexpressed in a resistant subline of GLC4. We conclude that overexpression of MRP cann ot account for all forms of non-Pgp MDR.