A multidrug resistance transporter from human MCF-7 breast cancer cells

Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70. doi: 10.1073/pnas.95.26.15665.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • 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

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • DNA Primers
  • Neoplasm Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Adenosine Triphosphate
  • Daunorubicin

Associated data

  • GENBANK/AF098951