Immunohistochemical Analysis of P-Glycoprotein Expression in Normal and Tumor Tissues in Humans

Abstract

Multidrug resistance (MDR) is the term used to describe the phenomenon whereby tumor cells in culture, selected for resistance to a single natural-product cytotoxic agent, simultaneously develop broad cross-resistance to a variety of structurally and functionally unrelated compounds (Biedler and Riehm, 1970). Recently, the identification and characterization of a human multidrug resistance gene (MDR1) and its product (gpl70, or P-glycoprotein) have been associated with the MDR phenotype (Ling and Thompson, 1974; Bech-Hansen et al., 1976; Juliano and Ling, 1976; Kartner et al., 1983) (see Part II of this book). P-glycoprotein is a transmembrane protein, expressed on the plasma membrane of certain normal and tumor cells (Thiebaut et al., 1987, 1989; Fojo et al., 1987b; Sugawara et al., 1988a,b; Cordon-Cardo et al., 1989a). High homology of this protein with bacterial transport proteins has been established, consistent with a function for P-glycoprotein as an energy-dependent efflux pump responsible for decreased drug accumulation in MDR tumor cells (Chen et al., 1986; Gerlach et al., 1986; Gros et al., 1986; Ueda et al., 1986; Hamada and Tsuruo, 1986).