title: A multidrug resistance transporter from human MCF-7 breast cancer cells.
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.
authors.affiliation: Greenebaum Cancer Center of the University of Maryland, Baltimore MD 21201, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Doyle
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: L V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: T
authors.initials: T
authors.lastname: Krogmann
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: A K
authors.initials: AK
authors.lastname: Rishi
authors.forename: D D
authors.initials: DD
authors.lastname: Ross
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D017931:DNA Primers; D003630:Daunorubicin / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D005260:Female; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012984:Software; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D017931:DNA Primers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D003630:Daunorubicin