Multidrug Resistance in Cancer: Genetics of ABC Transporters

Abstract

Multidrug resistance in human cancer is the major obstacle to long‐term, sustained response of a patient to chemotherapy. It has been convincingly documented that several adenosine triphosphate‐binding cassette transporters cause multidrug resistance in cancer cells by actively extruding the clinically administered chemotherapeutic drugs.

Keywords: cancer; chemotherapy; drug response; ABC transporter; pharmacogenomics

Figure 1.

Schematic illustration of ABCB1 (P‐glycoprotein (P‐gp)/MDR1), ABCC1 (MRP1), ABCC2 (MRP2/cMOAT) and ABCG2 (BCRPz/MXR1/ABCP).

Figure 2.

Phylogenetic tree of ABCC subfamily members.

Figure 3.

Three different modes in ABCC1‐mediated transport of xeno‐ and endobiotics: (a) transport of GSH conjugates; (b) transport of multivalent organic anions; (c) cotransport of drugs with GSH. GSH: glutathione; GS‐DNP: dinitrophenyl‐S‐glutathione conjugate; PGA1: prostaglandin A1; LTC4: leukotriene C4; GSSG: glutathione disulfide; BSP: bromosulfophthalein; ATP: adenosine triphosphate; ADP: adenosine diphosphate; Pi: inorganic phosphate.

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References

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Further Reading

Borst P, Evers R, Kool M and Wijnholds J (1999) The multidrug resistance protein family. Biochimica et Biophysica Acta 1461: 347–357.

Bunting KD (2002) ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20: 11–20.

Hoffmeyer S, Burk O, von Richter O, et al. (2000) Functional polymorphisms of the human multidrug‐resistance gene: multiple sequence variations and correlation of one allele with P‐glycoprotein expression and activity in vivo. Proceedings of the National Academy of Sciences of the United States of America 97: 3473–3478.

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Paulusma CC, Bosma PJ, Zaman GJR, et al. (1996) Congenital jaundice in rats with a mutation in a multidrug resistance‐associated protein gene. Science 271: 1126–1128.

Wada M, Toh S, Taniguchi K, et al. (1998) Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin–Johnson syndrome. Human Molecular Genetics 7: 203–207.

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Zhou S, Schuetz JD, Bunting KD, et al. (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side‐population phenotype. Nature Medicine 7: 1028–1034.

Web Links

HGNC Gene Family Nomenclature. Human ABC transporter genes http://www.gene.ucl.ac.uk/nomenclature/genefamily/abc.html

ATP‐binding cassette, sub‐family B (MDR/TAP), member 1 (ABCB1); Locus ID: 5243. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5243

ATP‐binding cassette, sub‐family B (MDR/TAP), member 4 (ABCB4); Locus ID: 5244. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5244

ATP‐binding cassette, sub‐family C (CFTR/MRP), member 1 (ABCC1); Locus ID: 4363. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4363

ATP‐binding cassette, sub‐family C (CFTR/MRP), member 2 (ABCC2); Locus ID: 1244. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1244

ATP‐binding cassette, sub‐family G (WHITE), member 2 (ABCG2); Locus ID: 9429. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=9429

ATP‐binding cassette, sub‐family B (MDR/TAP), member 1 (ABCB1); MIM number: 171050. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?171050

ATPhyphen;binding cassette, sub‐family B (MDR/TAP), member 4 (ABCB4); MIM number: 171060. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?171060

ATPhyphen;binding cassette, sub‐family C (CFTR/MRP), member 1 (ABCC1); MIM number: 158343. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?158343

ATPhyphen;binding cassette, sub‐family C (CFTR/MRP), member 2 (ABCC2); MIM number: 601107. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?601107

ATPhyphen;binding cassette, sub‐family G (WHITE), member 2 (ABCG2); MIM number: 603756. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?603756

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How to Cite close
Ishikawa, Toshihisa(Jan 2006) Multidrug Resistance in Cancer: Genetics of ABC Transporters. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006083]