ABCG2: structure, function and role in drug response.
ABCG2 was discovered in multi-drug-resistant cancer cells, with the identification of chemotherapeutic agents, such as mitoxantrone, flavopiridol, methotrexate and irinotecan as substrates. Later, drugs from other therapeutic groups were also described as substrates, including antibiotics, antivirals, HMG-CoA reductase inhibitors and flavonoids. An expanding list of compounds inhibiting ABCG2 has also been generated. The wide variety of drugs transported by ABCG2 and its normal tissue distribution with highest levels in the placenta, intestine and liver, suggest a role in protection against xenobiotics. ABCG2 also has an important role in the pharmacokinetics of its substrates. Single nucleotide polymorphisms of the gene were shown to alter either plasma concentrations of substrate drugs or levels of resistance against chemotherapeutic agents in cell lines. ABCG2 was also described as the determinant of the side population of stem cells. All these aspects of the transporter warrant further research aimed at understanding ABCG2's structure, function and regulation of expression.
Polgar
Orsolya
O
National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, NIH, 9000 Rockville Pike, Building 10, Room 13N240, Bethesda, MD 20892, USA.
Robey
Robert W
RW
Bates
Susan E
SE
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011487:Protein Conformation; D009626:Terminology as Topic
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins