SEQUENTIAL COEXPRESSION OF THE MULTIDRUG-RESISTANCE GENES MRP AND MDR1 AND THEIR PRODUCTS IN VP-16 (ETOPOSIDE)-SELECTED H69 SMALL-CELL LUNG-CANCER CELLS

Resistance to drugs included in the multidrug-resistance phenotype has been attributed to overexpression of either mdr1 or MRP genes and the ir products in numerous cell lines, while coexpression, to our knowled ge, has not previously been reported in the same cells. Human small ce ll lung cancer H69/VP cells were developed by continuous incubation in increasing doses of VP-16. In reverse transcription-PCR assays we fou nd over-expression of both mdr1 and multidrug-resistance protein (MRP) genes, and immunoblots showed both elevated P-glycoprotein and MRP in H69/VP cells. Double immunocytochemical staining demonstrated the exp ression of both MRP and P-glycoprotein in the same cells, indicating t hat the observations do not result from the selection of two independe nt clones. Examination of early passages of H69/VP cells showed that o ver-expression of MRP mRNA occurred prior to mdr1. Thus, cell lines an d clinical samples in the future should be tested for both mdr1/P-glyc oprotein and MRP since a positive result for one of the phenotypes doe s not preclude the existence of the other.