663
Views
89
CrossRef citations to date
0
Altmetric
Research Article

Pharmacogenomics of MRP Transporters (ABCC1-5) and BCRP (ABCG2)

&
Pages 317-354 | Published online: 09 Oct 2008

REFERENCES

  • Adachi M., Sampath J., Lan L. B., Sun D., Hargrove P., Flatley R., et al. Expression of MRP4 confers resistance to ganciclovir and compromises bystander cell killing. J. Biol. Chem. 2002; 277: 38998–39004
  • Anderson P. L., Lamba J., Aquilante C. L., Schuetz E., Fletcher C. V. Pharmacogenetic Characteristics of Indinavir, Zidovudine, and Lamivudine Therapy in HIV-Infected Adults: A Pilot Study. J. Acquir. Immune Defic. Syndr. 2006; 42: 441–449
  • Backstrom G., Taipalensuu J., Melhus H., Brandstrom H., Svensson A. C., Artursson P., et al. Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population. Eur J Pharm Sci 2003; 18: 359–364
  • Bakos E., Evers R., Sinko E., Varadi A., Borst P., Sarkadi B. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol. Pharmacol. 2000; 57: 760–768
  • Borst P., de Wolf C., van de Wetering K. Multidrug resistance-associated proteins 3, 4, and 5. Pflügers Arch 2007; 453: 661–673
  • Bosch T. M., Doodeman V. D., Smits P. H., Meijerman I., Schellens J. H., Beijnen J. H. Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a Dutch population. Mol Diagn Ther 2006; 10: 175–185
  • Bosch T. M., Kjellberg L. M., Bouwers A., Koeleman B. P., Schellens J. H., Beijnen J. H., et al. Detection of single nucleotide polymorphisms in the ABCG2 gene in a Dutch population. Am J Pharmacogenomics 2005; 5: 123–131
  • Chen Z. S., Lee K., Kruh G. D. Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J. Biol. Chem. 2001; 276: 33747–33754
  • Choi J. H., Ahn B. M., Yi J., Lee J. H., Nam S. W., Chon C. Y., et al. MRP2 haplotypes confer differential susceptibility to toxic liver injury. Pharmacogenet. Genomics 2007; 17: 403–415
  • Choudhuri S., Klaassen C. D. Structure, Function, Expression, Genomic Organization, and Single Nucleotide Polymorphisms of Human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) Efflux Transporters. Int. J. Toxicol. 2006; 25: 231–259
  • Cole S. P., Bhardwaj G., Gerlach J. H., Mackie J. E., Grant C. E., Almquist K. C., et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992; 258: 1650–1654
  • Colombo S., Soranzo N., Rotger M., Sprenger R., Bleiber G., Furrer H., et al. Influence of ABCB1, ABCC1, ABCC2, and ABCG2 haplotypes on the cellular exposure of nelfinavir in vivo. Pharmacogenet. Genomics 2005; 15: 599–608
  • Conrad S., Kauffmann H. M., Ito K., Deeley R. G., Cole S. P., Schrenk D. Identification of human multidrug resistance protein 1 (MRP1) mutations and characterization of a G671V substitution. J. Hum. Genet. 2001; 46: 656–663
  • Conrad S., Kauffmann H. M., Ito K., Leslie E. M., Deeley R. G., Schrenk D., et al. A naturally occurring mutation in MRP1 results in a selective decrease in organic anion transport and in increased doxorubicin resistance. Pharmacogenetics 2002; 12: 321–330
  • Corpechot C., Ping C., Wendum D., Matsuda F., Barbu V., Poupon R. Identification of a novel 974C–>G nonsense mutation of the MRP2/ABCC2 gene in a patient with Dubin-Johnson syndrome and analysis of the effects of rifampicin and ursodeoxycholic acid on serum bilirubin and bile acids. Am J Gastroenterol 2006; 101: 2427–2432
  • Cui Y., Konig J., Buchholz J. K., Spring H., Leier I., Keppler D. Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol. Pharmacol. 1999; 55: 929–937
  • Cusatis G., Gregorc V., Li J., Spreafico A., Ingersoll R. G., Verweij J., et al. Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J. Natl. Cancer. Inst. 2006; 98: 1739–1742
  • Dazert P., Meissner K., Vogelgesang S., Heydrich B., Eckel L., Bohm M., et al. Expression and localization of the multidrug resistance protein 5 (MRP5/ABCC5), a cellular export pump for cyclic nucleotides, in human heart. Am. J. Pathol. 2003; 163: 1567–1577
  • de Jong F. A., Marsh S., Mathijssen R. H., King C., Verweij J., Sparreboom A., et al. ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin. Cancer Res. 2004; 10: 5889–5894
  • de Jong F. A., Scott-Horton T. J., Kroetz D. L., McLeod H. L., Friberg L. E., Mathijssen R. H., et al. Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein. Clin. Pharmacol. Ther. 2007; 81: 42–49
  • Deeley R. G., Cole S. P. Substrate recognition and transport by multidrug resistance protein 1 (ABCC1). FEBS Lett 2006; 580: 1103–1111
  • Denk G. U., Soroka C. J., Takeyama Y., Chen W. S., Schuetz J. D., Boyer J. L. Multidrug resistance-associated protein 4 is up-regulated in liver but down-regulated in kidney in obstructive cholestasis in the rat. J. Hepatol. 2004; 40: 585–591
  • Dobbs N. A., Twelves C. J., Gillies H., James C. A., Harper P. G., Rubens R. D. Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry. Cancer Chemother. Pharmacol. 1995; 36: 473–476
  • Doerfel C., Rump A., Sauerbrey A., Gruhn B., Zintl F., Steinbach D. In acute leukemia, the polymorphism -211C>T in the promoter region of the multidrug resistance-associated protein 3 (MRP3) does not determine the expression level of the gene. Pharmacogenet. Genomics 2006; 16: 149–150
  • Evers R., de Haas M., Sparidans R., Beijnen J., Wielinga P. R., Lankelma J., et al. Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br. J. Cancer 2000; 83: 375–383
  • Faneyte I. F., Kristel P. M., van de Vijver M. J. Multidrug resistance associated genes MRP1, MRP2 and MRP3 in primary and anthracycline exposed breast cancer. Anticancer Res. 2004; 24: 2931–2939
  • Fetsch P. A., Abati A., Litman T., Morisaki K., Honjo Y., Mittal K., et al. Localization of the ABCG2 mitoxantrone resistance–associated protein in normal tissues. Cancer Lett. 2006; 235: 84–92
  • Flens M. J., Zaman G. J., van der Valk P., Izquierdo M. A., Schroeijers A. B., Scheffer G. L., et al. Tissue distribution of the multidrug resistance protein. Am. J. Pathol. 1996; 148: 1237–1247
  • Fromm M. F. Importance of P–glycoprotein at blood-tissue barriers. Trends Pharmacol. Sci. 2004; 25: 423–429
  • Fukushima-Uesaka H., Saito Y., Maekawa K., Hasegawa R., Suzuki K., Yanagawa T., et al. Genetic variations of the ABC transporter gene ABCC3 in a Japanese population. Drug Metab. Pharmacokinet. 2007a; 22: 129–135
  • Fukushima-Uesaka H., Saito Y., Tohkin M., Maekawa K., Hasegawa R., Kawamoto M., et al. Genetic variations and haplotype structures of the ABC transporter gene ABCC1 in a Japanese population. Drug Metab. Pharmacokinet. 2007b; 22: 48–60
  • Giessmann T., Modess C., Hecker U., Zschiesche M., Dazert P., Kunert-Keil C., et al. CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects. Clin. Pharmacol. Ther. 2004; 75: 213–222
  • Gradhand U., Lang T., Schaeffeler E., Glaeser H., Tegude H., Klein K., et al. Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Pharmacogenomics J. 2008; 8: 42–52
  • Gradhand U., Tegude H., Burk O., Eichelbaum M., Fromm M. F., Konig J. Functional analysis of the polymorphism -211C>T in the regulatory region of the human ABCC3 gene. Life Sci. 2007; 80: 1490–1494
  • Haenisch S., Mossiaguine I., Siegmund W., Cascorbi I. Frequency of single nucleotide polymorphisms in the MRP2 gene in healthy German subjects. European Journal of Clinical Pharmacology 2002; 58: S95
  • Haenisch S., Zimmermann U., Dazert E., Wruck C. J., Dazert P., Siegmund W., et al. Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex. Pharmacogenomics J. 2007; 7: 56–65
  • Haimeur A., Conseil G., Deeley R. G., Cole S. P. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr. Drug. Metab. 2004; 5: 21–53
  • Hashimoto K., Uchiumi T., Konno T., Ebihara T., Nakamura T., Wada M., et al. Trafficking and functional defects by mutations of the ATP-binding domains in MRP2 in patients with Dubin-Johnson syndrome. Hepatology 2002; 36: 1236–1245
  • Henriksen U., Gether U., Litman T. Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2. J Cell Sci. 2005; 118: 1417–1426
  • Hirano M., Maeda K., Matsushima S., Nozaki Y., Kusuhara H., Sugiyama Y. Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol. Pharmacol. 2005; 68: 800–807
  • Hirouchi M., Suzuki H., Itoda M., Ozawa S., Sawada J., Ieiri I., et al. Characterization of the cellular localization, expression level, and function of SNP variants of MRP2/ABCC2. Pharm. Res. 2004; 21: 742–748
  • Huang L., Wang Y., Grimm S. ATP-dependent transport of rosuvastatin in membrane vesicles expressing breast cancer resistance protein. Drug. Metab. Dispos. 2006; 34: 738–742
  • Hulot J. S., Villard E., Maguy A., Morel V., Mir L., Tostivint I., et al. A mutation in the drug transporter gene ABCC2 associated with impaired methotrexate elimination. Pharmacogenet. Genomics 2005; 15: 277–285
  • Ieiri I., Suzuki H., Kimura M., Takane H., Nishizato Y., Irie S., et al. Influence of common variants in the pharmacokinetic genes (OATP-C, UGT1A1, and MRP2) on serum bilirubin levels in healthy subjects. Hepatol. Res. 2004; 30: 91–95
  • Imai Y., Asada S., Tsukahara S., Ishikawa E., Tsuruo T., Sugimoto Y. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol. Pharmacol. 2003; 64: 610–618
  • Imai Y., Nakane M., Kage K., Tsukahara S., Ishikawa E., Tsuruo T., et al. C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Mol. Cancer Ther. 2002; 1: 611–616
  • Ito K., Oleschuk C. J., Westlake C., Vasa M. Z., Deeley R. G., Cole S. P. Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity. J. Biol. Chem. 2001a; 276: 38108–38114
  • Ito K., Olsen S. L., Qiu W., Deeley R. G., Cole S. P. Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J. Biol. Chem. 2001b; 276: 15616–15624
  • Ito K., Suzuki H., Horie T., Sugiyama Y. Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport. Pharm. Res. 2005; 22: 1559–1577
  • Ito S., Ieiri I., Tanabe M., Suzuki A., Higuchi S., Otsubo K. Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics 2001; 11: 175–184
  • Itoda M., Saito Y., Shirao K., Minami H., Ohtsu A., Yoshida T., et al. Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotacan. Drug Metab. Pharmacokinet. 2003; 18: 212–217
  • Itoda M., Saito Y., Soyama A., Saeki M., Murayama N., Ishida S., et al. Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: an association between single nucleotide polymorphisms in the 5¢-untranslated region and exon 28. Drug. Metab. Dispos. 2002; 30: 363–364
  • Izzedine H., Hulot J. S., Villard E., Goyenvalle C., Dominguez S., Ghosn J., et al. Association between ABCC2 Gene Haplotypes and Tenofovir-Induced Proximal Tubulopathy. J. Infect. Dis. 2006; 194: 1481–1491
  • Jada S. R., Lim R., Wong C. I., Shu X., Lee S. C., Zhou Q., et al. Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. 2007; 98: 1461–1467
  • Janneh O., Owen A., Chandler B., Hartkoorn R. C., Hart C. A., Bray P. G., et al. Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. Aids 2005; 19: 2097–2102
  • Janvilisri T., Shahi S., Venter H., Balakrishnan L., van Veen H. W. Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem. J. 2005; 385: 419–426
  • Janvilisri T., Venter H., Shahi S., Reuter G., Balakrishnan L., van Veen H. W. Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J. Biol. Chem. 2003; 278: 20645–20651
  • Jedlitschky G., Leier I., Buchholz U., Hummel-Eisenbeiss J., Burchell B., Keppler D. ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem. J. 1997; 327(Pt 1)305–310
  • Jedlitschky G., Tirschmann K., Lubenow L. E., Nieuwenhuis H. K., Akkerman J. W., Greinacher A., et al. The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage. Blood 2004; 104: 3603–3610
  • Kage K., Tsukahara S., Sugiyama T., Asada S., Ishikawa E., Tsuruo T., et al. Dominant-negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S-S dependent homodimerization. Int. J. Cancer 2002; 97: 626–630
  • Kartenbeck J., Leuschner U., Mayer R., Keppler D. Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin-Johnson syndrome. Hepatology 1996; 23: 1061–1066
  • Kawabata S., Oka M., Shiozawa K., Tsukamoto K., Nakatomi K., Soda H., et al. Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem. Biophys. Res. Commun. 2001; 280: 1216–1223
  • Keitel V., Burdelski M., Warskulat U., Kuhlkamp T., Keppler D., Haussinger D., et al. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Hepatology 2005; 41: 1160–1172
  • Keitel V., Kartenbeck J., Nies A. T., Spring H., Brom M., Keppler D. Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome. Hepatology 2000; 32: 1317–1328
  • Keitel V., Nies A. T., Brom M., Hummel-Eisenbeiss J., Spring H., Keppler D. A common Dubin-Johnson syndrome mutation impairs protein maturation and transport activity of MRP2 (ABCC2). Am. J. Physiol. Gastrointest. Liver. Physiol. 2003; 284: G: 165–174
  • Kerb R. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006; 234: 4–33
  • Kobayashi D., Ieiri I., Hirota T., Takane H., Maegawa S., Kigawa J., et al. Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug. Metab. Dispos. 2005; 33: 94–101
  • Koepsell H., Schmitt B. M., Gorboulev V. Organic cation transporters. Rev Physiol Biochem Pharmacol 2003; 150: 36–90
  • Kondo C., Suzuki H., Itoda M., Ozawa S., Sawada J., Kobayashi D., et al. Functional analysis of SNPs variants of BCRP/ABCG2. Pharm. Res. 2004; 21: 1895–1903
  • König J., Hartel M., Nies A. T., Martignoni M. E., Guo J., Buchler M. W., et al. Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. Int. J. Cancer 2005; 115: 359–367
  • König J., Seithel A., Gradhand U., Fromm M. F. Pharmacogenomics of human OATP transporters. Naunyn Schmiedeberg's Arch. Pharmacol. 2006; 372: 432–443
  • Kool M., van der Linden M., de Haas M., Scheffer G. L., de Vree J. M., Smith A. J., et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc. Natl. Acad. Sci. U S A 1999; 96: 6914–6919
  • Kubota H., Ishihara H., Langmann T., Schmitz G., Stieger B., Wieser H. G., et al. Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis. Epilepsy Res. 2006; 68: 213–228
  • Lamba J. K., Adachi M., Sun D., Tammur J., Schuetz E. G., Allikmets R., et al. Nonsense mediated decay downregulates conserved alternatively spliced ABCC4 transcripts bearing nonsense codons. Hum. Mol. Genet. 2003; 12: 99–109
  • Lang T., Hitzl M., Burk O., Mornhinweg E., Keil A., Kerb R., et al. Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver. Pharmacogenetics 2004; 14: 155–164
  • Le Saux O., Urban Z., Tschuch C., Csiszar K., Bacchelli B., Quaglino D., et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 2000; 25: 223–227
  • Lee K., Klein-Szanto A. J., Kruh G. D. Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells. J. Natl. Cancer. Inst. 2000; 92: 1934–1940
  • Lee Y. M., Cui Y., König J., Risch A., Jäger B., Drings P., et al. Identification and functional characterization of the natural variant MRP3-Arg1297His of human multidrug resistance protein 3 (MRP3/ABCC3). Pharmacogenetics 2004; 14: 213–223
  • Leggas M., Adachi M., Scheffer G. L., Sun D., Wielinga P., Du G., et al. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol. Cell Biol. 2004; 24: 7612–7621
  • Leier I., Jedlitschky G., Buchholz U., Center M., Cole S. P., Deeley R. G., et al. ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. Biochem. J. 1996; 314(Pt 2)433–437
  • Leier I., Jedlitschky G., Buchholz U., Cole S. P., Deeley R. G., Keppler D. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J. Biol. Chem. 1994; 269: 27807–27810
  • Leschziner G. D., Andrew T., Pirmohamed M., Johnson M. R. ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research. Pharmacogenomics J. 2007; 7: 154–179
  • Leslie E. M., Letourneau I. J., Deeley R. G., Cole S. P. Functional and structural consequences of cysteine substitutions in the NH2 proximal region of the human multidrug resistance protein 1 (MRP1/ABCC1). Biochemistry 2003; 42: 5214–5224
  • Leslie E. M., Mao Q., Oleschuk C. J., Deeley R. G., Cole S. P. Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase activities by interaction with dietary flavonoids. Mol. Pharmacol. 2001; 59: 1171–1180
  • Letourneau I. J., Deeley R. G., Cole S. P. Functional characterization of non-synonymous single nucleotide polymorphisms in the gene encoding human multidrug resistance protein 1 (MRP1/ABCC1). Pharmacogenet. Genomics 2005; 15: 647–657
  • Letourneau I. J., Slot A. J., Deeley R. G., Cole S. P. Mutational Analysis of a Highly Conserved Proline Residue in Mrp1, Mrp2 and Mrp3 Reveals a Partially Conserved Function. Drug. Metab. Dispos. 2007; 35: 1372–1379
  • Li J., Cusatis G., Brahmer J., Sparreboom A., Robey R. W., Bates S. E., et al. Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients. Cancer Biol. Ther. 2007; 6: 432–438
  • Loe D. W., Deeley R. G., Cole S. P. Verapamil stimulates glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). J. Pharmacol. Exp. Ther. 2000; 293: 530–538
  • Loos W. J., Gelderblom H., Verweij J., van Boven-van Zomeren D. M., Nooter K., Stoter G., et al. Red blood cells: a neglected compartment in topotecan pharmacokinetic analysis. Anticancer Drugs 2003; 14: 227–232
  • Maliepaard M., Scheffer G. L., Faneyte I. F., van Gastelen M. A., Pijnenborg A. C., Schinkel A. H., et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 2001; 61: 3458–3464
  • Marzolini C., Paus E., Buclin T., Kim R. B. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther. 2004a; 75: 13–33
  • Marzolini C., Tirona R. G., Kim R. B. Pharmacogenomics of the OATP and OAT families. Pharmacogenomics. 2004b; 5: 273–282
  • Meier Y., Pauli-Magnus C., Zanger U. M., Klein K., Schaeffeler E., Nussler A. K., et al. Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology 2006; 44: 62–74
  • Meissner K., Heydrich B., Jedlitschky G., Meyer Zu Schwabedissen H., Mosyagin I., Dazert P., et al. The ATP-binding cassette transporter ABCG2 (BCRP), a marker for side population stem cells, is expressed in human heart. J. Histochem. Cytochem. 2006; 54: 215–221
  • Merino G., Alvarez A. I., Pulido M. M., Molina A. J., Schinkel A. H., Prieto J. G. Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug. Metab. Dispos. 2006; 34: 690–695
  • Merino G., van Herwaarden A. E., Wagenaar E., Jonker J. W., Schinkel A. H. Sex-dependent expression and activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP/ABCG2) in liver. Mol. Pharmacol. 2005; 67: 1765–1771
  • Meyer zu Schwabedissen H. E., Jedlitschky G., Gratz M., Haenisch S., Linnemann K., Fusch C., et al. Variable expression of MRP2 (ABCC2) in human placenta: influence of gestational age and cellular differentiation. Drug. Metab. Dispos. 2005; 33: 896–904
  • Mizuarai S., Aozasa N., Kotani H. Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2. Int. J. Cancer 2004; 109: 238–246
  • Mor-Cohen R., Zivelin A., Rosenberg N., Goldberg I., Seligsohn U. A novel ancestral splicing mutation in the multidrug resistance protein 2 gene causes Dubin-Johnson syndrome in Ashkenazi Jewish patients. Hepatol. Res. 2005; 31: 104–111
  • Mor-Cohen R., Zivelin A., Rosenberg N., Shani M., Muallem S., Seligsohn U. Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome. J. Biol. Chem. 2001; 276: 36923–36930
  • Morisaki K., Robey R. W., Ozvegy-Laczka C., Honjo Y., Polgar O., Steadman K., et al. Single nucleotide polymorphisms modify the transporter activity of ABCG2. Cancer Chemother. Pharmacol. 2005; 56: 161–172
  • Moriya Y., Nakamura T., Horinouchi M., Sakaeda T., Tamura T., Aoyama N., et al. Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects. Biol Pharm Bull 2002; 25: 1356–1359
  • Niemi M., Arnold K. A., Backman J. T., Pasanen M. K., Godtel-Armbrust U., Wojnowski L., et al. Association of genetic polymorphism in ABCC2 with hepatic multidrug resistance-associated protein 2 expression and pravastatin pharmacokinetics. Pharmacogenet. Genomics 2006; 16: 801–808
  • Niemi M., Schaeffeler E., Lang T., Fromm M. F., Neuvonen M., Kyrklund C., et al. High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics 2004; 14: 429–440
  • Nies A. T., Jedlitschky G., König J., Herold-Mende C., Steiner H. H., Schmitt H. P., et al. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience 2004; 129: 349–360
  • Nies A. T., Keppler D. The apical conjugate efflux pump ABCC2 (MRP2). Pflügers Arch. 2006
  • Nies A. T., Spring H., Thon W. F., Keppler D., Jedlitschky G. Immunolocalization of multidrug resistance protein 5 in the human genitourinary system. J. Urol. 2002; 167: 2271–2275
  • Norris M. D., Smith J., Tanabe K., Tobin P., Flemming C., Scheffer G. L., et al. Expression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro. Mol. Cancer Ther. 2005; 4: 547–553
  • Oleschuk C. J., Deeley R. G., Cole S. P. Substitution of Trp1242 of TM17 alters substrate specificity of human multidrug resistance protein 3. Am. J. Physiol. Gastrointest. Liver. Physiol. 2003; 284(G)280–289
  • Paulusma C. C., Kool M., Bosma P. J., Scheffer G. L., ter Borg F., Scheper R. J., et al. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology 1997; 25: 1539–1542
  • Perdu J., Germain D. P. Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1) genes at locus 16p13.1 and exclusion of both genes as responsible for pseudoxanthoma elasticum. Hum Mutat 2001; 17: 74–75
  • Plasschaert S. L., de Bont E. S., Boezen M., vander Kolk D. M., Daenen S. M., Faber K. N., et al. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin. Cancer Res. 2005; 11: 8661–8668
  • Qian Y. M., Song W. C., Cui H., Cole S. P., Deeley R. G. Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1. J. Biol. Chem. 2001; 276: 6404–6411
  • Rao V. V., Dahlheimer J. L., Bardgett M. E., Snyder A. Z., Finch R. A., Sartorelli A. C., et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc. Natl. Acad. Sci. U S A 1999; 96: 3900–3905
  • Rau T., Erney B., Gores R., Eschenhagen T., Beck J., Langer T. High-dose methotrexate in pediatric acute lymphoblastic leukemia: impact of ABCC2 polymorphisms on plasma concentrations. Clin. Pharmacol. Ther. 2006; 80: 468–476
  • Reid G., Wielinga P., Zelcer N., De Haas M., Van Deemter L., Wijnholds J., et al. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol. Pharmacol. 2003a; 63: 1094–1103
  • Reid G., Wielinga P., Zelcer N., van der Heijden I., Kuil A., de Haas M., et al. The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc. Natl. Acad. Sci. U S A 2003b; 100: 9244–9249
  • Rigato I., Pascolo L., Fernetti C., Ostrow J. D., Tiribelli C. The human multidrug-resistance-associated protein MRP1 mediates ATP-dependent transport of unconjugated bilirubin. Biochem. J. 2004; 383: 335–341
  • Risch A., Müller P., Asher N., Bar-Cohen S., Bartsch H., Rund D. Polymorphisms in transporter genes and chemotherapy response in acute myeloid leukemia (AML) patients from Israel. Naunyn Schmiedeberg's Arch. Pharmacol. 2006; 372(supplement 1), 144 (abstract)
  • Ritter C. A., Jedlitschky G., Meyer zu Schwabedissen H., Grube M., Kock K., Kroemer H. K. Cellular export of drugs and signaling molecules by the ATP-binding cassette transporters MRP4 (ABCC4) and MRP5 (ABCC5). Drug Metab Rev 2005; 37: 253–278
  • Rius M., Nies A. T., Hummel-Eisenbeiss J., Jedlitschky G., Keppler D. Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology 2003; 38: 374–384
  • Rizwan A. N., Burckhardt G. Organic anion transporters of the SLC22 family: biopharmaceutical, physiological, and pathological roles. Pharm. Res. 2007; 24: 450–470
  • Robey R. W., Honjo Y., Morisaki K., Nadjem T. A., Runge S., Risbood M., et al. Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br. J. Cancer 2003; 89: 1971–1978
  • Rothnie A., Callaghan R., Deeley R. G., Cole S. P. Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1). J. Biol. Chem. 2006; 281: 13906–13914
  • Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., et al. Identification of 779 genetic variations in eight genes encoding members of the ATP-binding cassette, subfamily C (ABCC/MRP/CFTR). J.Hum. Genet. 2002; 47: 147–171
  • Sandusky G. E., Mintze K. S., Pratt S. E., Dantzig A. H. Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays. Histopathology 2002; 41: 65–74
  • Schaub T. P., Kartenbeck J., Konig J., Vogel O., Witzgall R., Kriz W., et al. Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J. Am. Soc. Nephrol. 1997; 8: 1213–1221
  • Scheffer G. L., Kool M., de Haas M., de Vree J. M., Pijnenborg A. C., Bosman D. K., et al. Tissue distribution and induction of human multidrug resistant protein 3. Lab. Invest. 2002a; 82: 193–201
  • Scheffer G. L., Pijnenborg A. C., Smit E. F., Muller M., Postma D. S., Timens W., et al. Multidrug resistance related molecules in human and murine lung. J. Clin. Pathol. 2002b; 55: 332–339
  • Schellens J. H., Maliepaard M., Scheper R. J., Scheffer G. L., Jonker J. W., Smit J. W., et al. Transport of topoisomerase I inhibitors by the breast cancer resistance protein. Potential clinical implications. Ann. N Y Acad. Sci. 2000; 922: 188–194
  • Schuetz E. G., Strom S., Yasuda K., Lecureur V., Assem M., Brimer C., et al. Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J. Biol. Chem. 2001; 276: 39411–39418
  • Schuetz J. D., Connelly M. C., Sun D., Paibir S. G., Flynn P. M., Srinivas R. V., et al. MRP4: A previously unidentified factor in resistance to nucleoside–based antiviral drugs. Nat. Med. 1999; 5: 1048–1051
  • Schwab M., Eichelbaum M., Fromm M. F. Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev. Pharmacol. Toxicol. 2003; 43: 285–307
  • Shoda J., Suzuki H., Sugiyama Y., Hirouchi M., Utsunomiya H., Oda K., et al. Novel mutations identified in the human multidrug resistance-associated protein 2 (MRP2/ABCC2) gene in a Japanese patient with Dubin-Johnson syndrome. Hepatol. Res. 2003; 27: 323–326
  • Soranzo N., Cavalleri G. L., Weale M. E., Wood N. W., Depondt C., Marguerie R., et al. Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene. Genome Res 2004; 14: 1333–1344
  • Sparreboom A., Gelderblom H., Marsh S., Ahluwalia R., Obach R., Principe P., et al. Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clin. Pharmacol. Ther. 2004; 76: 38–44
  • Sparreboom A., Loos W. J., Burger H., Sissung T. M., Verweij J., Figg W. D., et al. Effect of ABCG2 genotype on the oral bioavailability of topotecan. Cancer Biol. Ther. 2005; 4: 650–658
  • Steinbach D., Lengemann J., Voigt A., Hermann J., Zintl F., Sauerbrey A. Response to chemotherapy and expression of the genes encoding the multidrug resistance-associated proteins MRP2, MRP3, MRP4, MRP5, and SMRP in childhood acute myeloid leukemia. Clin. Cancer Res. 2003a; 9: 1083–1086
  • Steinbach D., Wittig S., Cario G., Viehmann S., Mueller A., Gruhn B., et al. The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype. Blood 2003b; 102: 4493–4498
  • Stojic J., Stohr H., Weber B. H. Three novel ABCC5 splice variants in human retina and their role as regulators of ABCC5 gene expression. BMC Mol. Biol. 2007; 8: 42
  • St-Pierre M. V., Serrano M. A., Macias R. I., Dubs U., Hoechli M., Lauper U., et al. Expression of members of the multidrug resistance protein family in human term placenta. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 279: R1495–1503
  • Suzuki H., Sugiyama Y. Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition. Adv. Drug. Deliv. Rev. 2002; 54: 1311–1331
  • Tamura A., Wakabayashi K., Onishi Y., Takeda M., Ikegami Y., Sawada S., et al. Re-evaluation and functional classification of non-synonymous single nucleotide polymorphisms of the human ATP-binding cassette transporter ABCG2. Cancer Sci. 2007; 98: 231–239
  • Tamura A., Watanabe M., Saito H., Nakagawa H., Kamachi T., Okura I., et al. Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: identification of alleles that are defective in porphyrin transport. Mol. Pharmacol. 2006; 70: 287–296
  • Tate G., Li M., Suzuki T., Mitsuya T. A new mutation of the ATP-binding cassette, sub-family C, member 2 (ABCC2) gene in a Japanese patient with Dubin-Johnson syndrome. Genes Genet Syst 2002; 77: 117–121
  • Toh S., Wada M., Uchiumi T., Inokuchi A., Makino Y., Horie Y., et al. Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am J Hum Genet 1999; 64: 739–746
  • Torky A. R., Stehfest E., Viehweger K., Taege C., Foth H. Immuno-histochemical detection of MRPs in human lung cells in culture. Toxicology 2005; 207: 437–450
  • van Aubel R. A., Smeets P. H., Peters J. G., Bindels R. J., Russel F. G. The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J. Am. Soc. Nephrol. 2002; 13: 595–603
  • van Aubel R. A., Smeets P. H., van den Heuvel J. J., Russel F. G. Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites. Am. J. Physiol. Renal Physiol. 2005; 288: F: 327–333
  • Vethanayagam R. R., Wang H., Gupta A., Zhang Y., Lewis F., Unadkat J. D., et al. Functional analysis of the human variants of breast cancer resistance protein: I206L, N590Y, and D620N. Drug. Metab. Dispos. 2005; 33: 697–705
  • Vogelgesang S., Kunert-Keil C., Cascorbi I., Mosyagin I., Schroder E., Runge U., et al. Expression of multidrug transporters in dysembryoplastic neuroepithelial tumors causing intractable epilepsy. Clin. Neuropathol. 2004; 23: 223–231
  • Wall A. M., Gajjar A., Link A., Mahmoud H., Pui C. H., Relling M. V. Individualized methotrexate dosing in children with relapsed acute lymphoblastic leukemia. Leukemia 2000; 14: 221–225
  • Wang H., Hao B., Zhou K., Chen X., Wu S., Zhou G., et al. Linkage disequilibrium and haplotype architecture for two ABC transporter genes (ABCC1 and ABCG2) in Chinese population: implications for pharmacogenomic association studies. Ann Hum Genet 2004; 68: 563–573
  • Wang X., Furukawa T., Nitanda T., Okamoto M., Sugimoto Y., Akiyama S., et al. Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol. Pharmacol. 2003; 63: 65–72
  • Wang X., Nitanda T., Shi M., Okamoto M., Furukawa T., Sugimoto Y., et al. Induction of cellular resistance to nucleoside reverse transcriptase inhibitors by the wild-type breast cancer resistance protein. Biochem. Pharmacol. 2004; 68: 1363–1370
  • Wang Z., Wang B., Tang K., Lee E. J., Chong S. S., Lee C. G. A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Hum. Mol. Genet. 2005; 14: 2075–2087
  • Wielinga P. R., Reid G., Challa E. E., van der Heijden I., van Deemter L., de Haas M., et al. Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells. Mol. Pharmacol. 2002; 62: 1321–1331
  • Wielinga P. R., van der Heijden I., Reid G., Beijnen J. H., Wijnholds J., Borst P. Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells. J. Biol. Chem. 2003; 278: 17664–17671
  • Wijnholds J., Mol C. A., van Deemter L., de Haas M., Scheffer G. L., Baas F., et al. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc. Natl. Acad. Sci. U S A 2000; 97: 7476–7481
  • Wojnowski L., Kulle B., Schirmer M., Schluter G., Schmidt A., Rosenberger A., et al. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 2005; 112: 3754–3762
  • Yanase K., Tsukahara S., Mitsuhashi J., Sugimoto Y. Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. Cancer Lett. 2006; 234: 73–80
  • Zamber C. P., Lamba J. K., Yasuda K., Farnum J., Thummel K., Schuetz J. D., et al. Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics 2003; 13: 19–28
  • Zamek-Gliszczynski M. J., Nezasa K. I., Tian X., Bridges A. S., Lee K., Belinsky M. G., et al. Evaluation of the Role of Multidrug Resistance-Associated Protein (Mrp) 3 and Mrp4 in Hepatic Basolateral Excretion of Sulfate and Glucuronide Metabolites of Acetaminophen, 4-Methylumbelliferone, and Harmol in Abcc3-/- and Abcc4-/- Mice. J. Pharmacol. Exp. Ther. 2006; 319: 1485–1491
  • Zelcer N., Reid G., Wielinga P., Kuil A., van der Heijden I., Schuetz J. D., et al. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem. J. 2003; 371: 361–367
  • Zelcer N., Saeki T., Reid G., Beijnen J. H., Borst P. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J. Biol.Chem. 2001; 276: 46400–46407
  • Zelcer N., van de Wetering K., de Waart R., Scheffer G. L., Marschall H. U., Wielinga P. R., et al. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J. Hepatol. 2006; 44: 768–775
  • Zelcer N., van de Wetering K., Hillebrand M., Sarton E., Kuil A., Wielinga P. R., et al. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc. Natl. Acad. Sci. U S A 2005; 102: 7274–7279
  • Zhang D. W., Cole S. P., Deeley R. G. Determinants of the substrate specificity of multidrug resistance protein 1: role of amino acid residues with hydrogen bonding potential in predicted transmembrane helix 17. J. Biol. Chem. 2002; 277: 20934–20941
  • Zhang D. W., Gu H. M., Vasa M., Muredda M., Cole S. P., Deeley R. G. Characterization of the role of polar amino acid residues within predicted transmembrane helix 17 in determining the substrate specificity of multidrug resistance protein 3. Biochemistry 2003; 42: 9989–10000
  • Zhang W., Yu B. N., He Y. J., Fan L., Li Q., Liu Z. Q., et al. Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clin. Chim. Acta 2006; 373: 99–103

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.