Sequential Coexpression of the Multidrug Resistance Genes MRP and mdrl and Their Products in VP-16 (Etoposide)-selected H69 Small Cell Lung Cancer Cells1

Resistance to drugs included in the multidrug-resistance phenotype has been attributed to overexpression of either mdrl or MRP genes and their products in numerous cell lines, while coexpression, to our knowledge, has not previously been reported in the same cells. Human small cell lung cancer H69/VP cells were developed by continuous incubation in increas ing doses of VP-16. In reverse transcription-PCR assays we found overexpression of both unit I and multidrug-resistance protein (MRP) genes, and immunoblots showed both elevated P-glycoprotein and MRP in H69/VP cells. Double immunocytochemical staining demonstrated the expression of both MRP and P-glycoprotein in the same cells, indicating that the observations do not result from the selection of two independent clones. Examination of early passages of H69/VP cells showed that overexpression of MRP in UNA occurred prior to mdrl. Thus, cell lines and clinical samples in the future should be tested for both mdrl/P-glycoprotein and MRP since a positive result for one of the phenotypes does not preclude the existence of the other.