Introduction

P-glycoprotein is a member of a small gene family. Humans have two genes, MDR1 and MDR3, while mice and hamsters have three each, mdr1, mdr2, and mdr3 in mice and pgp1, pgp2 and pgp3 in hamsters. Of these, only MDR1 in humans, mdr1 and mdr3 (mdr1a and mdr1b) in mice and pgp1 and pgp2 in hamsters can confer the multidrug resistance phenotype (Chin et al, 1989; Ng et al., 1989).

P-glycoprotein is a 170–180 kDa plasma membrane phosphoprotein that mediates multidrug resistance in mammalian cells. It functions as an energy-dependent drug efflux pump, extruding a wide range of compounds from the inside of cells.

Originally identified in multidrug resistant cells, expression of this protein has been demonstrated in a wide variety of cell lines and normal tissues, with a distribution that betrays a normal role in drug detoxification (Fojo et al., 1987; Thiebaut et al., 1987; Sugawara et al., 1988). Elegant studies in knockout mice have furthered our understanding of the roles of these proteins, and these will be discussed further below (Schinkel et al., 1994). The goal of exploiting our increasing understanding of this complex protein in the treatment of human cancer still remains in its infancy, a testament to the time required to translate laboratorystudies to clinical practice.