Role of the breast cancer resistance protein (ABCG2) in drug transport

AAPS J. 2005 May 11;7(1):E118-33. doi: 10.1208/aapsj070112.


The 72-kDa breast cancer resistance protein (BCRP) is the second member of the subfamily G of the human ATP binding cassette (ABC) transporter superfamily and thus also designated as ABCG2. Unlike P-glycoprotein and MRP1, which are arranged in 2 repeated halves, BCRP is a half-transporter consisting of only 1 nucleotide binding domain followed by 1 membrane-spanning domain. Current experimental evidence suggests that BCRP may function as a homodimer or homotetramer. Overexpression of BCRP is associated with high levels of resistance to a variety of anticancer agents, including anthracyclines, mitoxantrone, and the camptothecins, by enhancing drug efflux. BCRP expression has been detected in a large number of hematological malignancies and solid tumors, indicating that this transporter may play an important role in clinical drug resistance of cancers. In addition to its role to confer resistance against chemotherapeutic agents, BCRP actively transports structurally diverse organic molecules, conjugated or unconjugated, such as estrone-3-sulfate, 17beta-estradiol 17-(beta-D-glucuronide), and methotrexate. BCRP is highly expressed in the placental syncytiotrophoblasts, in the apical membrane of the epithelium in the small intestine, in the liver canalicular membrane, and at the luminal surface of the endothelial cells of human brain microvessels. This strategic and substantial tissue localization indicates that BCRP also plays an important role in absorption, distribution, and elimination of drugs that are BCRP substrates. This review summarizes current knowledge of BCRP and its relevance to multidrug resistance and drug disposition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / classification
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / physiology*
  • Absorption
  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Biological Transport / physiology*
  • Brain / metabolism
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm
  • Humans
  • Mice
  • Mice, Knockout
  • Models, Molecular
  • Multigene Family
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / classification
  • Neoplasm Proteins / physiology*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / physiology
  • Organ Specificity
  • Protein Binding
  • Protein Structure, Tertiary
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tissue Distribution
  • Xenobiotics / pharmacokinetics


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcg2 protein, mouse
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Xenobiotics