Multidrug resistance and differentiation of tumor cells induced by P-glycoprotein

The MDR1/P-glycoprotein (Pgp) gene activation is an early event in establishment of the complex multidrug resistant (MDR) phenotype. MDR is associated with induction of the MDR gene transcription followed by translation and maturation of functional Pgp. This mechanism is up-regulated in mammalian tissues that execute of tumor cell specialized functions, implying a link between MDR and certain differentiation phenotypes. Emergence of MDR is mediated by activation of numerous signal transduction pathways including those that regulate differentiation. This review analyzed the mechanisms of coordinated regulation of differentiation during acquisition of Pgp-mediated MDR by tumor cell. We consider this problem important because conventional chemotherapeutic drugs may trigger tumor cell differentiation that, in turn, could induce the development of MDR phenotype.