581
Views
18
CrossRef citations to date
0
Altmetric
Review Article

Determinants of the activity and substrate recognition of breast cancer resistance protein (ABCG2)

, , &
Pages 459-474 | Received 20 Jan 2014, Accepted 19 May 2014, Published online: 18 Jul 2014

References

  • Ahmed-Belkacem A, Macalou S, Borrelli F, et al. (2007). Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors. J Med Chem 50:1933–1938
  • Ahmed-Belkacem A, Pozza A, Muñoz-Martínez F, et al. (2005). Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2. Cancer Res 65:4852–4860
  • Allen JD, van Dort SC, Buitelaar M, et al. (2003). Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res 63:1339–1344
  • Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH. (1999). The mouse bcrp1/mxr/abcp gene: Amplifcation and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res 59:4237–4241
  • Allen JD, Jackson SC, Schinkel AH. (2002a). A mutation hot spot in the Bcrp1 (Abcg2) multidrug transporter in mouse cell lines selected for doxorubicin resistance. Cancer Res 62:2294–2299
  • Allen JD, Schinkel AH. (2002). Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2). Mol Cancer Ther 1:427–434
  • Allen JD, van Loevezijn A, Lakhai JM, et al. (2002b). Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 1:417–425
  • An G, Gallegos J, Morris ME. (2011). The bioflavonoid kaempferol is an Abcg2 substrate and inhibits Abcg2-mediated quercetin efflux. Drug Metab Dispos 39:426–432
  • Bäckström G, Taipalensuu J, Melhus H, et al. (2003). Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population. Eur J Pharm Sci 18:359–364
  • Beéry E, Rajnai Z, Abonyi T, et al. (2012). ABCG2 modulates chlorothiazide permeability in vitro characterization of its interaction. Drug Metab Pharmacokinet 27:349–353
  • Bihorel S, Camenisch G, Lemaire M, Scherrmann J-M. (2007). Modulation of the brain distribution of imatinib and its metabolites in mice by valspodar, zosuquidar and elacridar. Pharm Res 24:1720–1728
  • Boumendjel A, Macalou S, Ahmed-Belkacem A, et al. (2007). Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2. Bioorg Med Chem 15:2892–2897
  • Breedveld P, Zelcer N, Pluim D, et al. (2004). Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: Potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res 64:5804–5811
  • Brooks T, Minderman H, O’Loughlin KL, et al. (2003). Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Mol Cancer Ther 2:1195–1205
  • Brooks TA, Kennedy DR, Gruol DJ, et al. (2004). Structure-activity analysis of taxane-based broad-spectrum multidrug resistance modulators. Anticancer Res 24:409–416
  • Cai X, Bikadi Z, Ni Z, et al. (2010). Role of basic residues within or near the predicted transmembrane helix 2 of the human breast cancer resistance protein in drug transport. J Pharmacol Exp Ther 333:670–681
  • Chen Y-N, Mickleys LA, Schwartz AM, et al. (1990). Characterization of adriamycin-resistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein. J Biol Chem 265:10073–10080
  • Chen Z-S, Robey RW, Belinsky MG, et al. (2003). Transport of methotrexate, methotrexate polyglutamates, and 17β-estradiol 17-(β-d-glucuronide) by ABCG2: Effects of acquired mutations at R482 on methotrexate transport. Cancer Res 63:4048–4054
  • Clark R, Kerr ID, Callaghan R. (2006). Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter. Br J Pharmacol 149:506–515
  • Conseil G, Deeley RG, Cole SPC. (2006). Functional importance of three basic residues clustered at the cytosolic interface of transmembrane helix 15 in the multidrug and organic anion transporter MRP1 (ABCC1). J Biol Chem 281:43–50
  • Cooray HC, Janvilisri T, van Veen HW, et al. (2004). Interaction of the breast cancer resistance protein with plant polyphenols. Biochem Biophys Res Commun 317:269–275
  • Cowan KH, Goldsmith ME, Levine RM, et al. (1982). Dihydrofolate reductase gene amplification and possible rearrangement in estrogen-responsive methotrexate-resistant human breast cancer cells. J Biol Chem 257:15079–15086
  • Cygalova LH, Hofman J, Ceckova M, Staud F. (2009). Transplacental pharmacokinetics of glyburide, rhodamine 123, and BODIPY FL Prazosin: Effect of drug efflux transporters and lipid solubility. J Pharmacol Exp Ther 331:1118–1125
  • Dai C, Tiwari AK, Wu C-P, et al. (2008). Lapatinib (tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer Res 68:7905–7914
  • Davidson AL, Sharma S. (1997). Mutation of a single MalK subunit severely impairs maltose transport activity in Escherichia coli. J Bacteriol 179:5458–5464
  • de Bruin M, Miyake K, Litman T, et al. (1999). Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett, 146:117–126
  • de Jong FA, Marsh S, Mathijssen RHJ, et al. (2004). ABCG2 pharmacogenetics: Ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin Cancer Res 10:5889–5894
  • de Wolf C, Jansen R, Yamaguchi H, et al. (2008). Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther 7:3092–3102
  • Dohse M, Scharenberg C, Shukla S, et al. (2010). Comparison of ATP-binding cassette transporter interactions with the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib. Drug Metabol Dispos 38:1371–1380
  • Doyle LA, Ross DD. (2003). Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 22:7340–7358
  • Doyle LA, Yang W, Abruzzo LV, et al. (1998). A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665–15670
  • Doyle LA, Yang W, Gao Y, et al. (1996). Novobiocin increases the accumulation of daunorubicin in an atypical multidrug-resistant breast cancer subline. Proc Am Soc Clin Oncol 15:398
  • Ebert B, Seidel A, Lampen A. (2005). Identification of BCRP as transporter of benzo [a] pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists. Access 26:1754–1763
  • Ebert B, Seidel A, Lampen A. (2007). Phytochemicals induce breast cancer resistance protein in Caco-2 cells and enhance the transport of benzo[a]pyrene-3-sulfate. Toxicol Sci 96:227–236
  • Ejendal KFK, Diop NK, Schweiger LC, Hrycyna CA. (2006). The nature of amino acid 482 of human ABCG2 affects substrate transport and ATP hydrolysis but not substrate binding. Protein Sci 15:1597–1607
  • Enokizono J, Kusuhara H, Ose A, et al. (2008). Quantitative investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds. Drug Metabol Dispos 36:995–1002
  • Enokizono J, Kusuhara H, Sugiyama Y. (2007). Effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of phytoestrogens. Mol. Pharmacol 72:967–975
  • Fairchild CR, Ivy SP, Whang-Peng J, et al. (1987). Isolation of amplified and overexpressed DNA sequences from adriamycin-resistant human breast cancer cells. Cancer Res 47:5141–5148
  • FDA. (2009). Guidance for industry. Assay Development for Immunogenicity Testing of Therapeutic Proteins. FDA, 1–55
  • FDA. (2012). Guidance for industry. Drug interaction studies — Study design, data analysis, implications for dosing, and labeling recommendations. FDA, 1–35
  • Gandhi YA, Morris ME. (2009). Structure–activity relationships and quantitative structure–activity relationships for breast cancer resistance protein (ABCG2). AAPS J 11:541–552
  • Giri N, Shaik N, Pan G, et al. (2008). Investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) on pharmacokinetics and central nervous system penetration of abacavir and zidovudine in the mouse. Drug Metabol Dispos 36:1476–1484
  • Gupta A, Zhang Y, Unadkat JD, Mao Q. (2004). HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther 310:334–341
  • Han Y, Riwanto M, Go M-L, Ee PLR. (2008). Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues. Eur J Pharm Sci 35:30–41
  • Hecht SS. (2000). Inhibition of carcinogenesis by isothiocyanates. Drug Metabol Rev 32:395–411
  • Henriksen U, Fog JU, Litman T, Gether U. (2005a). Identification of intra- and intermolecular disulfide bridges in the multidrug resistance transporter ABCG2. J Biol Chem 280:36926–36934
  • Henriksen U, Gether U, Litman T. (2005b). Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2. J Cell Sci 118:1417–1426
  • Higgins CF. (2007). Multiple molecular mechanisms for multidrug resistance transporters. Nature 446:749–757
  • Hirano M, Maeda K, Matsushima S, et al. (2005). Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol 68:800–807
  • Honjo Y, Hrycyna CA, Yan Q-W, et al. (2001). Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res 61:6635–6639
  • Honjo Y, Morisaki K, Huff LM, et al. (2002). Single-nucleotide polymorphism (SNP) analysis in the ABC half-transporter ABCG2 (MXR/BCRP/ABCP1). Cancer Biol Ther 1:696–702
  • Hou Y, Li C-Z, Palaniyandi K, et al. (2009). Effects of putative catalytic base mutation E211Q on ABCG2-mediated methotrexate transport. Biochemistry 48:9122–9131
  • Houghton PJ, Germain GS, Harwood FC, et al. (2004). Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res 64:2333–2337
  • Huang L, Wang Y, Grimm S. (2006). ATP-dependent transport of rosuvastatin in membrane vesicles expressing cancer resistance protein. Drug Metabol Dispos 34:738–742
  • Ifergan I, Shafran A, Jansen G, et al. (2004). Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression. A role for BCRP in cellular folate homeostasis. J Biol Chem 279:25527–25534
  • Iida A, Saito S, Sekine A, et al. (2002). Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. J Hum Genet 47:285–310
  • Imai Y, Asada S, Tsukahara S, et al. (2003). Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol 64:610–618
  • Imai Y, Tsukahara S, Asada S, Sugimoto Y. (2004). Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 64:4346–52
  • Imai Y, Tsukahara S, Ishikawa E, et al. (2002). Estrone and 17β-estradiol reverse breast cancer resistance protein-mediated multidrug resistance. Jpn J Cancer Res 93:231–235
  • Ishikawa T, Kasamatsu S, Hagiwara Y, et al. (2003). Expression and functional characterization of human ABC transporter ABCG2 variants in insect cells. Drug Metab Pharmacokinet 18:194–202
  • Itoda M, Aito YS, Hirao KS, et al. (2003). Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotacan. Drug Metabol Pharmacokinet 18:212–217
  • Janvilisri T, Shahi S, Venter H, et al. (2005). 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 385:419–426
  • Janvilisri T, Venter H, Shahi S, et al. (2003). Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem 278:20645–20651
  • Ji Y, Morris ME. (2005). Membrane transport of dietary phenethyl isothiocyanate by ABCG2 (breast cancer resistance protein). Mol Pharm 2:414–419
  • Jin J, Shahi S, Kang HK, et al. (2006). Metabolites of ginsenosides as novel BCRP inhibitors. Biochem Biophys Res Commun 345:1308–1314
  • Jonker JW, Buitelaar M, Wagenaar E, et al. (2002). The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci USA 99:15649–15654
  • Jonker JW, Merino G, Musters S, et al. (2005). The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med 11:127–129
  • Kage K, Fujita T, Sugimoto Y. (2005). Role of Cys-603 in dimer/oligomer formation of the breast cancer resistance protein BCRP/ABCG2. Cancer Sci 96:866–872
  • Kalgutkar AS, Feng B, Nguyen HT, et al. (2007). Role of transporters in the dispostion of the selective phosphodiesterase-4 inhibitor (+)-2-[4({[2-benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl-3-fluoro-phenoxy]-propionic acid in rat and human. Drug Metabol Dispos 35:2111–2118
  • Kawabata S, Oka M, Shiozawa K, et al. (2001). Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem Biophys Res Commun 280:1216–1223
  • Kim H-S, Sunwoo YE, Ryu JY, et al. (2007). The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. Br J Clin Pharmacol 64:645–654
  • Kitamura S, Maeda K, Wang Y, Sugiyama Y. (2008). Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metabol Dispos 36:2014–2023
  • Kobayashi D, Ieiri I, Hirota T, et al. (2005). Functional assesment of ABCG2 (BCRP) gene polymorphism to protein expression in human placenta. Drug Metabol Dispos 33:94–101
  • Komatani H, Kotani H, Hara Y, et al. (2001). Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res 61:2827–2832
  • Krishnamurthy P, Ross DD, Nakanishi T, et al. (2004). The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 279:24218–24225
  • Krishnamurthy P, Schuetz JD. (2005). The ABC transporter Abcg2/Bcrp: Role in hypoxia mediated survival. BioMetals 18:349–358
  • Lapinski PE, Neubig RR, Raghavan M. (2001). Walker A lysine mutations of TAP1 and TAP2 interfere with peptide translocation but not peptide binding. J Biol Chem 276:7526–7533
  • Li J, Cusatis G, Brahmer J, et al. (2007). Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients. Cancer Biol Ther 6:432–438
  • Lin X, Skolnik S, Chen X, Wang J. (2011). Attenuation of intestinal absorption by major efflux transporters: Quantitative tools and strategies using a Caco-2 model. Drug Metabol Dispos 39:265–274
  • Litman T, Brangi M, Hudson E, et al. (2000). The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 113:2011–2021
  • Liu X-L, Tee H-W, Go M-L. (2008a). Functionalized chalcones as selective inhibitors of P-glycoprotein and breast cancer resistance protein. Bioorg Med Chem 16:171–180
  • Liu Y, Yang Y, Qi J, et al. (2008b). Effect of cysteine mutagenesis on the function and disulfide bond formation of human ABCG2. J Pharmacol Exp Ther 326:33–40
  • Ma J, Maliepaard M, Nooter K, et al. (1998). Reduced cellular accumulation of topotecan: A novel mechanism of resistance in a human ovarian cancer cell line. Br J Cancer 77:1645–1652
  • Maliepaard M, van Gastelen MA, Tohgo A, et al. (2001). Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 7:935–941
  • Marquez B, van Bambeke F. (2011). ABC multidrug transporters: Target for modulation of drug pharmacokinetics and drug-drug interactions. Curr Drug Targets 12:600–620
  • Matsson P, Englund G, Ahlin G, et al. (2007). A global drug inhibition pattern for the human ATP-binding cassette transporter breast cancer resistance protein (ABCG2). J Pharmacol Exp Ther 323:19–30
  • Matsson P, Pedersen JM, Norinder U, et al. (2009). Identification of novel specific and general inhibitors of the three major human ATP-binding cassette transporters P-gp, BCRP and MRP2 among registered drugs. Pharm Res 26:1816–1831
  • McDevitt CA, Collins R, Kerr ID, Callaghan R. (2009). Purification and structural analyses of ABCG2. Adv Drug Deliv Rev 61:57–65
  • McDevitt CA, Crowley E, Hobbs G, et al. (2008). Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2? FEBS J 275:4354–4362
  • Merino G, Álvarez AI, Pulido MM, et al. (2006). Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug Metabol Dispos 34:690–695
  • Mitomo H, Kato R, Ito A, et al. (2003). A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: Critical role of arginine-482 in methotrexate transport. Biochem J 373:767–774
  • Miwa M, Tsukahara S, Ishikawa E, et al. (2003). Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants. Int J Cancer 107:757–763
  • Mizuarai S, Aozasa N, Kotani H. (2004). Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2. Int J Cancer 109:238–246
  • Mohrmann K, van Eijndhoven MAJ, Schinkel AH, Schellens JHM. (2005). Absence of N-linked glycosylation does not affect plasma membrane localization of breast cancer resistance protein (BCRP/ABCG2). Cancer Chemother Pharmacol 56:344–350
  • Muenster U, Grieshop B, Ickenroth K, Gnoth MJ. (2008). Characterization of substrates and inhibitors for the in vitro assessment of Bcrp mediated drug-drug interactions. Pharm Res 25:2320–2326
  • Müller M, Bakos É, Welker E, et al. (1996). Altered drug-stimulated ATPase activity in mutants of the human multidrug resistance protein. J Biol Chem 271:1877–1883
  • Nakagawa H, Saito H, Ikegami Y, et al. (2006). Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett 234:81–89
  • Ni Z, Bikadi Z, Rosenberg MF, Mao Q. (2010a). Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr Drug Metabol 11:603–617
  • Ni Z, Bikadi Z, Shuster DL, et al. (2011). Identification of proline residues in or near the transmembrane helices of the human breast cancer resistance protein (BCRP/ABCG2) that are important for transport activity and substrate specificity. Biochemistry 50:8057–8066
  • Ni Z, Mark ME, Cai X, Mao Q. (2010b). Fluorescence resonance energy transfer (FRET) analysis demonstrates dimer/oligomer formation of the human breast cancer resistance protein (BCRP/ABCG2) in intact cells. Int J Biochem Mol Biol 1:1–11
  • Özvegy C, Litman T, Szakács G, et al. (2001). Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun 285:111–117
  • Özvegy C, Váradi A, Sarkadi B. (2002). Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. J Biol Chem 277:47980–47990
  • Özvegy-Laczka C, Hegedüs T, Várady G, et al. (2004). High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol 65:1485–1495
  • Özvegy-Laczka C, Köblös G, Sarkadi B, Váradi A. (2005). Single amino acid (482) variants of the ABCG2 multidrug transporter: Major differences in transport capacity and substrate recognition. Biochim Biophys Acta 1668:53–63
  • Pal A, Mehn D, Molnar E, et al. (2007). Cholesterol potentiates ABCG2 activity in a heterologous expression system: Improved in vitro model to study function of human ABCG2. J Pharmacol Exp Ther 321:1085–1094
  • Pan G, Giri N, Elmquist WF. (2007). Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides abacavir and zidovudine. Drug Metab Dispos 35:1165–1173
  • Pavek P, Merino G, Wagenaar E, et al. (2005). Human breast cancer resistance protein: Interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther 312:144–152
  • Pick A, Müller H, Pajeva IK, et al. (2011). Structure–activity relationships of flavonoids as inhibitors of breast cancer resistance protein (BCRP). Bioorg Med Chem Elsevier Ltd 19:2090–2102
  • Polgar O, Robey RW, Morisaki K, et al. (2004). Mutational analysis of ABCG2: Role of the GXXXG motif. Biochemistry 43:9448–9456
  • Pozza A, Perez-Victoria JM, Sardo A, et al. (2006). Purification of breast cancer resistance protein ABCG2 and role of arginine-482. Cell Mol Life Sci 63:1912–1922
  • Rabindran SK, He H, Singh M, et al. (1998). Reversal of a novel multidrug resistance mechanism in human colon carcinoma cells by fumitremorgin C. Cancer Res 58:5850–5858
  • Rabindran SK, Ross DD, Doyle LA, et al. (2000). Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res 60:47–50
  • Rajendra R, Gounder MK, Saleem A, et al. (2003). Differential effects of the breast cancer resistance protein on the cellular accumulation and cytotoxicity of 9-aminocamptothecin and 9-nitrocamptothecin. Cancer Res 63:3228–3233
  • Robey RW, Honjo Y, Morisaki K, et al. (2003). Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br J Cancer 89:1971–1978
  • Robey RW, Honjo Y, van de Laar A, et al. (2001a). A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2). Biochim Biophys Acta 1512:171–182
  • Robey RW, Medina-Pérez WY, Nishiyama K, et al. (2001b). Overexpression of the ATP-binding cassette half-transporter, ABCG2 (MXR/BCRP/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res 2:145–152
  • Robey RW, Steadman K, Polgar O, Bates SE. (2005). ABCG2-mediated transport of photosensitizers. Cancer Biol Ther 4:187–194
  • Robey RW, Steadman K, Polgar O, et al. (2004). Pheophorbide a is a specific probe for ABCG2 function and inhibition. Cancer Res 64:1242–1246
  • Robey RW, To KKK, Polgar O, et al. (2009). ABCG2: A perspective. Adv Drug Deliv Rev 61:3–13
  • Rosenbach-Belkin V, Chen L, Fiedor L, et al. (1996). Serine conjugates of chlorophyll and bacteriochlorophyll: Photocytotoxicity in vitro and tissue distribution in mice bearing melanoma tumors. Photochem Photobiol 64:174–181
  • Rosenberg MF, Bikadi Z, Chan J, et al. (2010). The human breast cancer resistance protein (BCRP/ABCG2) shows conformational changes with mitoxantrone. Structure 18:482–493
  • Ross DD, Yang W, Abruzzo LV, et al. (1999). Atypical multidrug resistance: Breast cancer resistance protein messenger RNA in mitoxantrone-selected cell lines. J Natl Cancer Inst 91:429–433
  • Russ WP, Engelman DM. (2000). The GxxxG motif: A framework for transmembrane helix-helix association. J Mol Biol 296:911–919
  • Ryu S, Kawabe T, Nada S, Yamaguchi A. (2000). Identification of basic residues involved in drug export function of human multidrug resistance-associated protein 2. J Biol Chem 275:39617–39624
  • Saito H, Hirano H, Nakagawa H, et al. (2006). A new strategy of high-speed screening and quantitative structure-activity relationship analysis to evaluate human ATP-binding cassette transporter ABCG2-drug interactions. J Pharmacol Exp Ther 317:1114–1124
  • Scharenberg CW, Harkey MA, Torok-Storb B. (2002). The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99:507–512
  • Schneider E, Horton JK, Yang C-H, et al. (1994). Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. Cancer Res 54:152–158
  • Shigeta J, Katayama K, Mitsuhashi J, et al. (2010). BCRP/ABCG2 confers anticancer drug resistance without covalent dimerization. Cancer Sci 101:1813–1821
  • Shiozawa K, Oka M, Soda H, et al. (2004). Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer 108:146–151
  • Shukla S, Robey RW, Bates SE, Ambudkar SV. (2006). The calcium channel blockers, 1,4-dihydropyridines, are substrates of the multidrug resistance-linked ABC drug transporter, ABCG2. Biochemistry 45:8940–8951
  • Shukla S, Wu C-P, Nandigama K, Ambudkar SV. (2007). The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2. Mol Cancer Ther 6:3279–3286
  • Shukla S, Zaher H, Hartz A, et al. (2009). Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res 26:480–487
  • Staud F, Pavek P. (2005). Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol 37:720–725
  • Subczynski WK, Wisniewska A. (2000). Physical properties of lipid bilayer membranes: Relevance to biological functions. Acta Biochim Pol 47:613–622
  • Sugimoto Y, Tsukahara S, Imai Y, et al. (2003). Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther 2:105–112
  • Szabó K, Welker E, Bakos É, et al. (1998). Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1. J Biol Chem 273:10132–10138
  • Szczygieł M, Urbańska K, Jurecka P, et al. (2008). Central metal determines pharmacokinetics of chlorophyll-derived xenobiotics. J Med Chem 51:4412–4418
  • Taguchi Y, Kino K, Morishima M, et al. (1997). Alteration of substrate specificity by mutations at the His61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein. Biochemistry 36:8883–8889
  • Tamura A, Watanabe M, Saito H, et al. (2006). 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 70:287–296
  • Telbisz A, Müller M, Özvegy-Laczka C, et al. (2007). Membrane cholesterol selectively modulates the activity of the human ABCG2 multidrug transporter. Biochim Biophys Acta 1768:2698–2713
  • Valdameri G, Genoux-Bastide E, Peres B, et al. (2012a). Substituted chromones as highly potent nontoxic inhibitors, specific for the breast cancer resistance protein. J Med Chem 55:966–970
  • Valdameri G, Pereira Rangel L, Spatafora C, et al. (2012b). Methoxy stilbenes as potent, specific, untransported, and noncytotoxic inhibitors of breast cancer resistance protein. ACS Chem Biol 7:322–330
  • van de Wetering K, Burkon A, Feddema W, et al. (2009). Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol. Mol Pharmacol 75:876–885
  • van der Heijden J, de Jong MC, Dijkmans BAC, et al. (2004). Development of sulfasalazine resistance in human T cells induces expression of the multidrug resistance transporter ABCG2 (BCRP) and augmented production of TNFα. Ann Rheum Dis 63:138–144
  • van Hattum AH, Hoogsteen IJ, Schlüper HMM, et al. (2002). Induction of breast cancer resistance protein by the camptothecin derivative DX-8951f is associated with minor reduction of antitumour activity. Br J Cancer 87:665–672
  • van Herwaarden AE, Wagenaar E, Karnekamp B, et al. (2006). Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk. Carcinogenesis 27:123–130
  • van Herwaarden AE, Wagenaar E, Merino G, et al. (2007). Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. Mol Cell Biol 27:1247–1253
  • van Veen HW, Margolles A, Müller M, et al. (2000). The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism. EMBO J 19:2503–2514
  • Velamakanni S, Wei SL, Janvilisri T, van Veen HW. (2007). ABCG transporters: Structure, substrate specificities and physiological roles. J Bioenerg Biomembr 39:465–471
  • Vethanayagam R, Wang H, Gupta A, et al. (2005). Functional analysis of the human variants of breast cancer resistance protein: I206L, N590Y, and D620N. Drug Metab Dispos 33:697–705
  • Volk EL, Schneider E. (2003). Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res 63:5538–5543
  • Wang H, Lee E-W, Cai X, et al. (2009). Membrane topology of the human breast cancer resistance protein (BCRP/ABCG2) determined by epitope insertion and immunofluorescence. Biochemistry 47:13778–13787
  • Wang J-S, Zhu H-J, Markowitz JS, et al. (2008). Antipsychotic drugs inhibit the function of breast cancer resistance protein. Basic Clin Pharmacol Toxicol 103:336–341
  • Wang L, McNamara PJ. (2012). Stereoselective interaction of pantoprazole with ABCG2. I. Drug accumulation in rat milk. Drug Metab Dispos 40:1018–1023
  • Wierdl M, Wall A, Morton CL, et al. (2003). Carboxylesterase-mediated sensitization of human tumor cells to CPT-11 cannot override ABCG2-mediated drug resistance. Mol Pharmacol 64:279–288
  • Wiese M, Pajeva IK. (2001). Structure-activity relationships of multidrug resistance reversers. Curr Med Chem 8:685–713
  • Woodward OM, Köttgen A, Coresh J, et al. (2009). Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci USA 106:10338–10342
  • Xia CQ, Liu N, Miwa GT, Gan L-S. (2007). Interactions of cyclosporin A with breast cancer resistance protein. Drug Metab Dispos 35:576–582
  • Xu J, Peng H, Chen Q, et al. (2007). Oligomerization domain of the multidrug resistance-associated transporter ABCG2 and its dominant inhibitory activity. Cancer Res 67:4373–4381
  • Yanase K, Tsukahara S, Asada S, et al. (2004). Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol Cancer Ther 3:1119–1125
  • Yoshikawa M, Ikegami Y, Hayasaka S, et al. (2004). Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer 110:921–927
  • Zaher H, Khan AA, Palandra J, et al. (2006). Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalazine absorption and elimination in the mouse. Mol Pharm 3:55–61
  • Zhang S, Yang X, Morris ME. (2004a). Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 21:1263–1273
  • Zhang S, Yang X, Morris ME. (2004b). Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol 65:1208–1216
  • Zhang Y, Gupta A, Wang H, et al. (2005). BCRP transports dipyridamole and is inhibited by calcium channel blockers. Pharm Res 22:2023–2034
  • Zheng X, Morgan J, Pandey SK, et al. (2009). Conjugation of 2′-(1′-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo. J Med Chem 52:4306–4318
  • Zhou L, Naraharisetti SB, Wang H, et al. (2008). The breast cancer resistance protein (Bcrp1/Abcg2) limits fetal distribution of glyburide in the pregnant mouse: An Obstetric-Fetal Pharmacology Research Unit Network and University of Washington Specialized Center of Research Study. Mol Pharmacol 73:949–959
  • Zhou S, Zong Y, Ney PA, et al. (2005). Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels. Blood 105:2571–2576

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.