Intracellular expression of P-glycoprotein in a human colon tumor cell line.
A number of human tumor cell lines originating in tissues which normally express high levels of P-glycoprotein were examined for the expression of mdr-1 RNA and P-glycoprotein and their sensitivity to doxorubicin and vincristine. There was a wide variation in expression levels and in drug sensitivity among the cell lines. In the human colon tumor cell line, LS 174T, high levels of P-glycoprotein and mdr-1 RNA were observed, but this line was very sensitive to doxorubicin and vincristine. Immunoprecipitation of P-glycoprotein from preparations of membrane and cytoplasmic proteins and immunofluorescence studies using anti-P-glycoprotein antibodies revealed that P-glycoprotein in these cells is not associated with the plasma membrane, but is, instead, found intracellularly. These results emphasize the need for functional analysis of P-glycoprotein in cells that express this mediator of multidrug resistance.
Duensing
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Syntex Discovery Research, Palo Alto, CA 94304.
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014750:Vincristine; D012313:RNA; D004317:Doxorubicin; D014700:Verapamil