A multidrug resistance transporter from human MCF-7 breast cancer cells.
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.
Doyle
L A
LA
Greenebaum Cancer Center of the University of Maryland, Baltimore MD 21201, USA.
Yang
W
W
Abruzzo
L V
LV
Krogmann
T
T
Gao
Y
Y
Rishi
A K
AK
Ross
D D
DD
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
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