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Genetic basis of multidrug resistance of tumor cells

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Abstract

Multidrug resistance in animal cells is defined as the simultaneous resistance to a variety of compounds which appear to be structurally and mechanistically unrelated. One type of multidrug resistance is characterized by the decreased accumulation of hydrophobic natural product drugs, a phenotype which is mediated by an ATP-dependent integral membrane multidrug transporter termed P-glycoprotein or P170. The gene coding for P170 is calledMDR. The nucleotide-binding domain of P-glycoprotein shares sequence homology with a family of bacterial permease ATP-binding components. In addition, P170 as a whole is structurally very similar to a number of prokaryotic and eukaryotic proteins believed to be involved in transport activities. This review summarizes our current knowledge of the molecular biology and clinical significance ofMDR expression and P-glycoprotein transport activity, as well as some theories about the function of this protein in normal cells.

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  1. Susan E. Kane

    Present address: Division of Surgery, City of Hope Medical Center, 91010, Duarte, California

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  1. Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland

    Susan E. Kane & Michael M. Gottesman

  2. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland

    Ira Pastan

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Kane, S.E., Pastan, I. & Gottesman, M.M. Genetic basis of multidrug resistance of tumor cells. J Bioenerg Biomembr 22, 593–618 (1990). https://doi.org/10.1007/BF00762963

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