The role of half-transporters in multidrug resistance.
ATP-binding cassette proteins comprise a superfamily of transporter proteins, a subset of which have been implicated in multidrug resistance. Although P-glycoprotein was described over 15 years ago, the recent expansion in the number of transporters identified has prompted renewed interest in the role of drug transporters in clinical drug resistance. These newly identified transporters include additional members of the MRP family, ABC2, and a new half-transporter, MXR/BCRP/ABCP1. This half-transporter confers high levels of resistance to mitoxantrone, anthracyclines, and the camptothecins SN-38 and topotecan. At 72 kDa, MXR localizes to the plasma membrane in cells which highly overexpress the protein either through gene amplification or though gene rearrangement. Future studies will be aimed at identifying an inhibitor, and attempting to translate recognition of this new transporter into a target for anticancer treatment.
Bates
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Medicine Branch, National Cancer Institute, Bethesda, Maryland, USA. sebates@helix.nih.gov
Robey
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Miyake
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Rao
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Ross
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Litman
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D000818:Animals; D018432:Drug Resistance, Multiple / Q000502:physiology*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology*
D027425:ATP-Binding Cassette, Sub-Family C Proteins