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PMID:9861027

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Citation

Doyle, LA, Yang, W, Abruzzo, LV, Krogmann, T, Gao, Y, Rishi, AK and Ross, DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 95:15665-70

Abstract

MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.

Links

PubMed PMC28101

Keywords

ATP-Binding Cassette Transporters/biosynthesis; ATP-Binding Cassette Transporters/chemistry; ATP-Binding Cassette Transporters/genetics; Adenosine Triphosphate/metabolism; Amino Acid Sequence; Animals; Antineoplastic Agents/toxicity; Breast Neoplasms; Cell Survival/drug effects; Cloning, Molecular; DNA Primers; Daunorubicin/pharmacokinetics; Drug Resistance, Multiple; Female; Gene Library; Humans; Molecular Sequence Data; Neoplasm Proteins; Phylogeny; RNA, Messenger/genetics; Recombinant Proteins/biosynthesis; Recombinant Proteins/chemistry; Reverse Transcriptase Polymerase Chain Reaction; Software; Transcription, Genetic; Transfection; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ABCG2

enables

GO:0008559: ABC-type xenobiotic transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ABCG2

involved_in

GO:1990748: cellular detoxification

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ABCG2

enables

GO:0008559: xenobiotic transmembrane transporting ATPase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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