Amplification of the P-Glycoprotein Gene Family and Multidrug Resistance

Abstract

This chapter focuses on the role of amplification of the P-glycoprotein (Pgp) gene family in the expression of multidrug resistance (MDR) in a number of cultured mammalian cell lines. In this way, the pleiotropic nature of the MDR phenotype could be explained by differential amplification and/or expression of these genes. This hypothesis has been addressed by identifying genes that are coamplified in different MDR sublines and determining the correlation between gene amplification/expression and drug resistance. Coamplification of these genes implied that they may contribute to drug resistance. It is unlikely that this pattern of differential amplification is coincidental. Thus, coamplification of this gene may be fortuitous because it happens to be tightly linked to other Pgp genes that can confer drug resistance.