OVEREXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) INCREASES RESISTANCE TO NATURAL PRODUCT DRUGS

Amplification of the gene encoding multidrug resistance-associated pro tein (MRP) and overexpression of its cognate mRNA have been detected i n multidrug-resistant cell lines derived from several different tumor types. To establish whether or not the increase in MRP is responsible for drug resistance in these cell lines, we have transfected HeLa cell s with MRP expression vectors. The transfectants display an increase i n resistance to doxorubicin that is proportional to the levels of a M( r) 190,000, integral membrane protein recognized by anti-MRP antibodie s. The transfectants are also resistant to vincristine and VP-16 but n ot to cisplatin. The results demonstrate that MRP overexpression confe rs a multidrug resistance phenotype similar to that formerly associate d exclusively with elevated levels of P-glycoprotein.