Regulation of the multidrug resistance genes by stress signals

Abstract

Transporters in the body play a large role in the distribution and elimination of many clinically important therapeutic substances. Of these, perhaps the one that has been best studied is P-Glycoprotein (PGP), a 170 kDa membrane-bound protein which has been implicated as a primary cause of multidrug-resistance in tumors. An understanding of the physiological regulation of these transporters is key to designing strategies for the improvement of therapeutic efficacy of drugs which are their substrates. To that end, we examine herein the current state of understanding of the molecular regulation of PGP by a variety of endogenous and environmental stimuli which evoke stress responses including cytotoxic agents, heat shock, irradiation, genotoxic stress, inflammation, inflammatory mediators, cytokines and growth factors.