Expression of multidrug resistance protein-related genes in lung cancer: Correlation with drug response

Recently, cDNAs have been identified that encode four human proteins (MRP2- 5) with structural similarity to the multidrug resistance protein (MRP). Pr eliminary studies have shown that levels of mRNAs encoding MRP2, MRP3, and MRP5, are increased in some drug-selected cell lines, but the correlation o f MRP2-5 mRNA levels with drug resistance has not been examined. Using a co llection of small cell lung cancer (SCLC) and non-SCLC patient samples and unselected cell lines established from patients at various stages of treatm ent, we examined the expression of MRP2, MRP3, MRP4, and MRP5, as well as M DR1 and MRP, by PCR. The levels of individual mRNAs were correlated with th e sensitivity of these cell lines to doxorubicin (DOX), vincristine, VP-16, acid cis-diamminedichloroplatinum(II), as determined by a modified MTT ass ay. Using both SCLC and non-SCLC cell lines, we confirmed the previously ob served correlation of MRP mRNA levels with resistance to DOX (B. G. Camplin g et al., Clin. Cancer Res., 3:115-122, 1997) and found a strong correlatio n of MRP3 mRNA levels with resistance of the cell lines to DOX. In addition , the mRNA levels of both MRP and MRP3 correlated with resistance of the ce ll lines to vincristine, VP-16, and cis-diamminedichloroplatinum(II), These findings are consistent with the suggestion that MRP3, like MRP, may contr ibute to the drug resistance phenotype of lung cancer cells.