POSSIBLE INVOLVEMENT OF MULTIDRUG-RESISTANCE-ASSOCIATED PROTEIN (MRP)GENE-EXPRESSION IN SPONTANEOUS DRUG-RESISTANCE TO VINCRISTINE, ETOPOSIDE AND ADRIAMYCIN IN HUMAN GLIOMA-CELLS

The multidrug-resistance phenotype in human tumors is partly associate d with over-expression of the 170 kDa-P-glycoprotein encoded by the mu ltidrug-resistance-1 (MDR1) gene. Another related, but non-P-glycoprot ein, multidrug-resistance-associated protein (MRP) gene encodes a 190 kDa-membrane ATP-binding protein. Glioblastoma multiforme is a highly malignant primary neoplasm of the central nervous system which is refr actory to anti-cancer chemotherapy, but the mechanism underlying this drug resistance is unknown. Out of glioma cell lines, 2, namely IN500 and T98G, which had elevated MRP mRNA levels, showed the highest resis tance to multiple anti-cancer agents such as etoposide, vincristine an d adriamycin, and decreased intracellular accumulation of etoposide. I n the remaining 5 cell lines, various degrees of sensitivity to adriam ycin and etoposide appeared to correlate with their respective MRP mRN A levels. Our study proposes that MRP may be involved in spontaneous m ultidrug resistance in human gliomas. (C) 1994 Wiley-Liss, Inc.