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


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Article Info

DATE

2005-03

AUTHORS

Qingcheng Mao

ABSTRACT

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, 17β-estradiol 17-(β-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. More... »

PAGES

e118-e133

References to SciGraph publications

  • 2003-10-23. Multidrug resistance genes in infant acute lymphoblastic leukemia: Ara-C is not a substrate for the breast cancer resistance protein in LEUKEMIA
  • 2003-10-23. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2) in ONCOGENE
  • 2001-09. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype in NATURE MEDICINE
  • 2004-05-17. Subcellular localization of the ABCG2 transporter in normal and malignant human gallbladder epithelium in LABORATORY INVESTIGATION
  • 2003-11-11. Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity in BRITISH JOURNAL OF CANCER
  • 2001-12. Complete Characterization of the Human ABC Gene Family in JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
  • 2003-10-23. P-glycoprotein: from genomics to mechanism in ONCOGENE
  • 2004-06-21. Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function in LEUKEMIA
  • 2002-05-02. Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML) in LEUKEMIA
  • 2004-07. Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2001-12. The Role of Half-Transporters in Multidrug Resistance in JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
  • 2002-07-31. BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia in LEUKEMIA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1208/aapsj070112

    DOI

    http://dx.doi.org/10.1208/aapsj070112

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032127936

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/16146333


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