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AAPS J. Mar 2005; 7(1): E118–E133.
Published online May 11, 2005. doi:  10.1208/aapsj070112
PMCID: PMC2751502

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

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.

Keywords: BCRP, ATP-binding cassette, ABCG2, transporter, drug transport

References

1. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomies to mechanism. Oncogene. 2003;22:7468–7485. doi: 10.1038/sj.onc.1206948. [PubMed] [Cross Ref]
2. Haimeur A, Conseil G, Deeley RG, Cole SP. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab. 2004;5:21–53. doi: 10.2174/1389200043489199. [PubMed] [Cross Ref]
3. Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA. 1998;95:15665–15670. doi: 10.1073/pnas.95.26.15665. [PMC free article] [PubMed] [Cross Ref]
4. Miyake K, Mickley L, Litman T, et al. Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone resistant cells: demonstration of homology to ABC transport genes. Cancer Res. 1999;59:8–13. [PubMed]
5. Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 1998;58:5337–5339. [PubMed]
6. Rocchi E, Khodjakov A, Volk EL, et al. The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane. Biochem Biophys Res Commun. 2000;271:42–46. doi: 10.1006/bbrc.2000.2590. [PubMed] [Cross Ref]
7. Maliepaard M, Scheffer GL, Faneyte IF, et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 2001;61:3458–3464. [PubMed]
8. Allen JD, Schinkel AH. Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2) Mol Cancer Ther. 2002;1:427–434. [PubMed]
9. Doyle LA, Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2) Oncogene. 2003;22:7340–7358. doi: 10.1038/sj.onc.1206938. [PubMed] [Cross Ref]
10. Bates SE, Robey R, Miyake K, Rao K, Ross DD, Litman T. The role of half-transporters in multidrug resistance. J Bioenerg Biomembr. 2001;33:503–511. doi: 10.1023/A:1012879205914. [PubMed] [Cross Ref]
11. Dean M, Allikmets R. Complete characterization of the human ABC gene family. J Bioenerg Biomembr. 2001;33:475–479. doi: 10.1023/A:1012823120935. [PubMed] [Cross Ref]
12. Borst P, Elferink RO. Mammalian ABC transporters in health and disease. Annu Rev Biochem. 2002;71:537–592. doi: 10.1146/annurev.biochem.71.102301.093055. [PubMed] [Cross Ref]
13. Riordan JR. Cystic fibrosis as a disease of misprocessing of the cystic fibrosis transmembrane conductance regulator glycoprotein. Am J Hum Genet. 1999;64:1499–1504. doi: 10.1086/302429. [PMC free article] [PubMed] [Cross Ref]
14. Arnell H, Mantyjarvi M, Tuppurainen K, Andreasson S, Dahl N. Stargardt disease: linkage to the ABCR gene region on lp21-p22 in Scandinavian families. Acta Ophthalmol Scand. 1998;76:649–652. doi: 10.1034/j.1600-0420.1998.760602.x. [PubMed] [Cross Ref]
15. 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. [PubMed]
16. Klucken J, Buchler C, Orso E, et al. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc Natl Acad Sci USA. 2000;97:817–822. doi: 10.1073/pnas.97.2.817. [PMC free article] [PubMed] [Cross Ref]
17. Yu L, Bergmann K, Lutjohann D, Hobbs HH, Cohen JC. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. J Lipid Res. 2004;45:301–307. doi: 10.1194/jlr.M300377-JLR200. [PubMed] [Cross Ref]
18. Graf GA, Yu L, Li WP, et al. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem. 2003;278:48275–48282. doi: 10.1074/jbc.M310223200. [PubMed] [Cross Ref]
19. Yu L, Li-Hawkins J, Hammer RE, et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest. 2002;110:671–680. doi: 10.1172/JCI200216001. [PMC free article] [PubMed] [Cross Ref]
20. Xu J, Liu Y, Yang Y, Bates S, Zhang JT. Characterization of oligomeric human half ABC transporter ABCG2/BCRP/MXR/ABCP in plasma membranes. J Biol Chem. 2004;279:19781–19789. doi: 10.1074/jbc.M310785200. [PubMed] [Cross Ref]
21. Ozvegy C, Varadi A, Sarkadi B. Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. Modulation of substrate specificity by a point mutation. J Biol Chem. 2002;277:47980–47990. doi: 10.1074/jbc.M207857200. [PubMed] [Cross Ref]
22. Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, Veen HW. Sterol transport by the human breast cancer resistance protein (ABC G2) expressed in Lactococcus lactis. J Biol Chem. 2003;278:20645–20651. doi: 10.1074/jbc.M301358200. [PubMed] [Cross Ref]
23. Ross DD, Yang W, Abruzzo LV, et al. Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J Natl Cancer Inst. 1999;91:429–433. doi: 10.1093/jnci/91.5.429. [PubMed] [Cross Ref]
24. Maliepaard M, Gastelen MA, Jong LA, et al. Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999;59:4559–4563. [PubMed]
25. Yang CH, Schneider E, Kuo ML, Volk EL, Rocchi E, Chen YC. BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem Pharmacol. 2000;60:831–837. doi: 10.1016/S0006-2952(00)00396-8. [PubMed] [Cross Ref]
26. Ishii M, Iwahana M, Mitsui I, et al. Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug-resistant sublines including BCRP-mediated camptothecin derivative-resistant variantsderived from the human lung cancer cell line PC-6. Anticancer Drugs. 2000;11:353–362. doi: 10.1097/00001813-200006000-00005. [PubMed] [Cross Ref]
27. Robey RW, Medina-Perez WY, Nishiyama K, et al. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BC rp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res. 2001;7:145–152. [PubMed]
28. Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH. The mouse Berpl/Mxr/Abep gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res. 1999;59:4237–4241. [PubMed]
29. Eisenblatter T, Galla HJ. A new multidrug resistance protein at the blood-brain barrier. Biochem Biophys Res Commun. 2002;293:1273–1278. doi: 10.1016/S0006-291X(02)00376-5. [PubMed] [Cross Ref]
30. Eisenblatter T, Huwel S, Galla HJ. Characterisation of the brain multidrug resistance protein (BMDP/ABCG2/BCRP) expressed at the blood-brain barrier. Brain Res. 2003;971:221–231. doi: 10.1016/S0006-8993(03)02401-6. [PubMed] [Cross Ref]
31. Hori S, Ohtsuki S, Tachikawa M, et al. Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte-derived soluble factor(s) J Neurochem. 2004;90:526–536. doi: 10.1111/j.1471-4159.2004.02537.x. [PubMed] [Cross Ref]
32. Rajagopal A, Simon SM. Subcellular localization and activity of multidrug resistance proteins. Mol Biol Cell. 2003;14:3389–3399. doi: 10.1091/mbc.E02-11-0704. [PMC free article] [PubMed] [Cross Ref]
33. Cole SP, Chanda ER, Dicke FP, Gerlach JH, Mirski SE. Non-P-glycoprotein-mediated multidrug resistance in a small cell lung cancer cell line: evidence for decreased susceptibility to drug-induced DNA damage and reduced levels of topoisomerase II. Cancer Res. 1991;51:3345–3352. [PubMed]
34. Aust S, Obrist P, Jaeger W, et al. Subcellular localization of the ABCG2 transporter in normal and malignant human gallbladder epithelium. Lab Invest. 2004;84:1024–1036. doi: 10.1038/labinvest.3700127. [PubMed] [Cross Ref]
35. Litman T, Brangi M, Hudson E, et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2) J Cell Sci. 2000;113:2011–2021. [PubMed]
36. Robey RW, Honjo Y, Laar A, et al. A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2) Biochim Biophys Acta. 2001;1512:171–182. doi: 10.1016/S0005-2736(01)00308-X. [PubMed] [Cross Ref]
37. Minderman H, Suvannasankha A, O'Loughlin KL, et al. Flow cytometric analysis of breast cancer resistance protein expression and function. Cytometry. 2002;48:59–65. doi: 10.1002/cyto.10111. [PubMed] [Cross Ref]
38. Rabindran SK, Ross DD, Doyle LA, Yang W, Greenberger LM. Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res. 2000;60:47–50. [PubMed]
39. Hazlehurst LA, Foley NE, Gleason-Guzman MC, et al. Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226 myeloma cell line. Cancer Res. 1999;59:1021–1028. [PubMed]
40. Nakagawa M, Schneider E, Dixon KH, et al. Reduced intracellular drug accumulation in the abscence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells. Cancer Res. 1992;52:6175–6181. [PubMed]
41. Maliepaard M, Gastelen MA, Tohgo A, et al. 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. 2001;7:935–941. [PubMed]
42. Kawabata S, Oka M, Shiozawa K, et al. Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem Biophys Res Commun. 2001;280:1216–1223. doi: 10.1006/bbrc.2001.4267. [PubMed] [Cross Ref]
43. Nakatomi K, Yoshikawa M, Oka M, et al. Transport of 7-ethyl-10-hydroxycamptothecin (SN-38) by breast cancer resistance protein ABCG2 in human lung cancer cells. Biochem Biophys Res Commun. 2001;288:827–832. doi: 10.1006/bbrc.2001.5850. [PubMed] [Cross Ref]
44. Shiozawa K, Oka M, Soda H, et al. Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer. 2004;108:146–151. doi: 10.1002/ijc.11528. [PubMed] [Cross Ref]
45. Rajendra R, Gounder MK, Saleem A, et al. Differential effects of the breast cancer resistance protein on the cellular accumulation and cytotoxicity of 9-aminocamptothecin and 9-nitrocamptothecin. Cancer Res. 2003;63:3228–3233. [PubMed]
46. Bates SE, Medina-Perez WY, Kohlhagen G, et al. ABCG2 mediates differential resistance to SN-38 and homocamptothecins. J Pharmacol Exp Ther. 2004;310:836–842. doi: 10.1124/jpet.103.063149. [PubMed] [Cross Ref]
47. Yoshikawa M, Ikegami Y, Hayasaka S, et al. Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer. 2004;110:921–927. doi: 10.1002/ijc.20216. [PubMed] [Cross Ref]
48. Honjo Y, Hrycyna CA, Yan QW, et al. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res. 2001;61:6635–6639. [PubMed]
49. Nakanishi T, Karp JE, Tan M, et al. Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patients. Clin Cancer Res. 2003;9:3320–3328. [PubMed]
50. Volk EL, Farley KM, Wu Y, Li F, Robey RW, Schneider E. Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance. Cancer Res. 2002;62:5035–5040. [PubMed]
51. Chen Z-S, Robey RW, Belinsky MG, et al. Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003;63:4048–4054. [PubMed]
52. Robey RW, Honjo Y, Morisaki K, et al. Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br J Cancer. 2003;89:1971–1978. doi: 10.1038/sj.bjc.6601370. [PMC free article] [PubMed] [Cross Ref]
53. Miwa M, Tsukahara S, Ishikawa E, Asada S, Imai Y, Sugimoto Y. Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants. Int J Cancer. 2003;107:757–763. doi: 10.1002/ijc.11484. [PubMed] [Cross Ref]
54. Kim M, Turnquist H, Jackson J, et al. The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res. 2002;8:22–28. [PubMed]
55. Scharenberg CW, Harkey MA, Torok-Storb B. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood. 2002;99:507–512. doi: 10.1182/blood.V99.2.507. [PubMed] [Cross Ref]
56. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y. ABC G2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003;278:22644–22649. doi: 10.1074/jbc.M212399200. [PubMed] [Cross Ref]
57. 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. doi: 10.1124/mol.64.3.610. [PubMed] [Cross Ref]
58. Ifergan I, Shafran A, Jansen G, Hooijberg JH, Scheffer GL, Assaraf YG. Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression: Aa role for BCRP in cellular folate homeostasis. J Biol Chem. 2004;279:25527–25534. doi: 10.1074/jbc.M401725200. [PubMed] [Cross Ref]
59. Jonker JW, Buitelaar M, Wagenaar E, et al. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci USA. 2002;99:15449–15654. doi: 10.1073/pnas.202607599. [PMC free article] [PubMed] [Cross Ref]
60. Robey RW, Steadman K, Polgar O, et al. Pheophorbide a Is a Specific Probe for ABCG2 Function and Inhibition. Cancer Res. 2004;64:1242–1246. doi: 10.1158/0008-5472.CAN-03-3298. [PubMed] [Cross Ref]
61. Sinha R, Gustafson DR, Kulldorff M, Wen WQ, Cerhan JR, Zheng W. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a carcinogen in high-temperature-cooked meat, and breast cancer risk. J Natl Cancer Inst. 2000;92:1352–1354. doi: 10.1093/jnci/92.16.1352. [PubMed] [Cross Ref]
62. Herwaarden AE, Jonker JW, Wagenaar E, et al. The breast cancer resistance protein (Berpl/Abeg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res. 2003;63:6447–6452. [PubMed]
63. Woehlecke H, Pohl A, Alder-Baerens N, Lage H, Herrmann A. Enhanced exposure of phosphatidylserine in human gastric carcinoma cells overexpressing the half-size ABC transporter BCRP (ABCG2) Biochem J. 2003;376:489–495. doi: 10.1042/BJ20030886. [PMC free article] [PubMed] [Cross Ref]
64. Erlichman C, Boerner SA, Hallgren CG, et al. The HER tyrosine kinase inhibitor C11033 enhances cytotoxicity of 7-ethyl-10-hydroxy-camptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res. 2001;61:739–748. [PubMed]
65. Burger H, Tol H, Boersma AW, et al. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004;104:2940–2942. doi: 10.1182/blood-2004-04-1398. [PubMed] [Cross Ref]
66. Imai Y, Tsukahara S, Asada S, Sugimoto Y. Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res. 2004;64:4346–4352. doi: 10.1158/0008-5472.CAN-04-0078. [PubMed] [Cross Ref]
67. Polli JW, Baughman TM, Humphreys JE, et al. The systemic exposure of an N-methyl-d-aspartate receptor antagonist is limited in mice by the p-glycoprotein and breast cancer resistance protein efflux transporters. Drug Metab Dispos. 2004;32:722–726. doi: 10.1124/dmd.32.7.722. [PubMed] [Cross Ref]
68. Breedveld P, Zelcer N, Pluim D, et al. Mechanism of the pharmaco-kinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004;64:5804–5811. doi: 10.1158/0008-5472.CAN-03-4062. [PubMed] [Cross Ref]
69. Wang X, Furukawa T, Nitanda T, et al. Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003;63:65–72. doi: 10.1124/mol.63.1.65. [PubMed] [Cross Ref]
70. Wang X, Nitanda T, Shi M, 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. doi: 10.1016/j.bcp.2004.05.052. [PubMed] [Cross Ref]
71. Brangi M, Litman T, Ciotti M, et al. Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 1999;59:5938–5946. [PubMed]
72. Rabindran SK, He H, Singh M, et al. Reversal of a novel multidrug resistance mechanism in human colon carcinoma cells by fumitremorgin C. Cancer Res. 1998;58:5850–5858. [PubMed]
73. Sparreboom A, Gelderblom H, Marsh S, et al. Diflomotecan pharmacokinetics in relation to ABC G2 421C>A genotype. Clin Pharmacol Ther. 2004;76:38–44. doi: 10.1016/j.clpt.2004.03.003. [PubMed] [Cross Ref]
74. Volk EL, Schneider E. Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003;63:5538–5543. [PubMed]
75. Nakagawa R, Hara Y, Arakawa H, Nishimura S, Komatani H. ABCG2 confers resistance to indolocarbazole compounds by ATP-dependent transport. Biochem Biophys Res Commun. 2002;299:669–675. doi: 10.1016/S0006-291X(02)02712-2. [PubMed] [Cross Ref]
76. Komatani H, Kotani H, Hara Y, et al. 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. 2001;61:2827–2832. [PubMed]
77. Bruin M, Miyake K, Litman T, Robey R, Bates SE. Reversal of resistance by GF120918 in cell lines expressing the ABC Half-transporter. Cancer Lett. 1999;146:117–126. doi: 10.1016/S0304-3835(99)00182-2. [PubMed] [Cross Ref]
78. Allen JD, Loevezijn A, Lakhai JM, et al. 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. 2002;1:417–425. [PubMed]
79. Loevezijn A, Allen JD, Schinkel AH, Koomen GJ. Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines. Bioorg Med Chem Lett. 2001;11:29–32. doi: 10.1016/S0960-894X(00)00588-6. [PubMed] [Cross Ref]
80. Özvegy-Laczka C, Hegedus T, Varady G, et al. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol. 2004;65:1485–1495. doi: 10.1124/mol.65.6.1485. [PubMed] [Cross Ref]
81. Houghton PJ, Germain GS, Harwood FC, et al. Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res. 2004;64:2333–2337. doi: 10.1158/0008-5472.CAN-03-3344. [PubMed] [Cross Ref]
82. Yang CH, Chen YC, Kuo ML. Novobiocin sensitizes BCRP/MXR/ABCP overexpressing topotecan-resistant human breast carcinoma cells to topotecan and mitoxantrone. Anticancer Res. 2003;23:2519–2523. [PubMed]
83. Sugimoto Y, Tsukahara S, Imai Y, Ueda K, Tsuruo T. Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003;2:105–112. [PubMed]
84. Zhou S, Schuetz JD, Bunting KD, et al. The ABC transporter Bcrpl/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001;7:1028–1034. doi: 10.1038/nm0901-1028. [PubMed] [Cross Ref]
85. Minderman H, O'Loughlin KL, Pendyala L, Baer MR. VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin Cancer Res. 2004;10:1826–1834. doi: 10.1158/1078-0432.CCR-0914-3. [PubMed] [Cross Ref]
86. Woehlecke H, Osada H, Herrmann A, Lage H. Reversal of breast cancer resistance protein-mediated drug resistance by tryprostatin A. Int J Cancer. 2003;107:721–728. doi: 10.1002/ijc.11444. [PubMed] [Cross Ref]
87. Zhang S, Yang X, Morris ME. Flavonoids are inhibitors of breast cancer resistance protein (ABCG2) Mol Pharmacol. 2004;65:1208–1216. doi: 10.1124/mol.65.5.1208. [PubMed] [Cross Ref]
88. Cooray HC, Janvilisri T, Veen HW, Hladky SB, Barrand MA. Interaction of the breast cancer resistance protein with plant polyphenols. Biochem Biophys Res Commun. 2004;317:269–275. doi: 10.1016/j.bbrc.2004.03.040. [PubMed] [Cross Ref]
89. Gupta A, Zhang Y, Unadkat JD, Mao Q. HiV Protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2) J Pharmacol Exp Ther. 2004;310:334–341. doi: 10.1124/jpet.104.065342. [PubMed] [Cross Ref]
90. Allen JD, Dort SC, Buitelaar M, Tellingen O, Schinkel AH. Mouse breast cancer resistance protein (Berpl/Abeg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003;63:1339–1344. [PubMed]
91. Kruijtzer CM, Beijnen JH, Rosing H, et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol. 2002;20:2943–2950. doi: 10.1200/JCO.2002.12.116. [PubMed] [Cross Ref]
92. Jonker JW, Smit JW, Brinkhuis RF, et al. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst. 2000;92:1651–1656. doi: 10.1093/jnci/92.20.1651. [PubMed] [Cross Ref]
93. Allen JD, Jackson SC, Schinkel AH. A mutation hot spot in the Berpl (Abcg2) multidrug transporter in mouse cell lines selected for doxorubicin resistance. Cancer Res. 2002;62:2294–2299. [PubMed]
94. Alqawi O, Bates S, Georges E. Arginine 482 to threonine 482 mutation in breast cancer resistance protein (ABCG2) inhibits rhodaminel 23 transport while increasing binding. Biochem J. 2004;382:711–716. doi: 10.1042/BJ20040355. [PMC free article] [PubMed] [Cross Ref]
95. Zamber CP, Lamba JK, Yasuda K, 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. doi: 10.1097/00008571-200301000-00004. [PubMed] [Cross Ref]
96. Imai Y, Nakane M, Kage K, 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. [PubMed]
97. Honjo Y, Morisaki K, Huff LM, et al. Single-nucleotide polymorphism (SNP) analysis in the ABC half-transporter ABCG2 (MXR/BCRP/ABCP1) Cancer Biol Ther. 2002;1:696–702. [PubMed]
98. 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. doi: 10.1002/ijc.11669. [PubMed] [Cross Ref]
99. Kage K, Tsukahara S, Sugiyama 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. doi: 10.1002/ijc.10100. [PubMed] [Cross Ref]
100. Litman T, Jensen U, Hansen A, et al. Use of peptide antibodies to probe for the mitoxantrone resistance-associated protein MXR/BCRP/ABCP/ABCG2. Biochim Biophys Acta. 2002;1565:6–16. doi: 10.1016/S0005-2736(02)00492-3. [PubMed] [Cross Ref]
101. Mao Q, Conseil G, Gupta A, Cole SP, Unadkat JD. Functional expression of the human breast cancer resistance protein in Pichia pastoris. Biochem Biophys Res Commun. 2004;320:730–737. doi: 10.1016/j.bbrc.2004.06.012. [PubMed] [Cross Ref]
102. Mitomo H, Kato R, Ito A, et al. A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem J. 2003;373:767–774. doi: 10.1042/BJ20030150. [PMC free article] [PubMed] [Cross Ref]
103. Polgar O, Robey RW, Morisaki K, et al. Mutational analysis of ABCG2: role of the GXXXG motif. Biochemistry. 2004;43:9448–9456. doi: 10.1021/bi0497953. [PubMed] [Cross Ref]
104. Ozvegy C, Litman T, Szakacs G, et al. Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001;285:111–117. doi: 10.1006/bbrc.2001.5130. [PubMed] [Cross Ref]
105. Ross DD, Karp JE, Chen TT, Doyle LA. Expression of breast cancer resistance protein in blast cells from patients with acute leukemia. Blood. 2000;96:365–368. [PubMed]
106. Steinbach D, Sell W, Voigt A, Hermann J, Zintl F, Sauerbrey A. BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia. Leukemia. 2002;16:1443–1447. doi: 10.1038/sj.leu.2402541. [PubMed] [Cross Ref]
107. Plasschaert SL, Kolk DM, Bont ES, Vellenga E, Kamps WA, Vries EG. Breast cancer resistance protein (BCRP) in acute leukemia. Leuk Lymphoma. 2004;45:649–654. doi: 10.1080/10428190310001597928. [PubMed] [Cross Ref]
108. Abbott BL, Colapietro AM, Barnes Y, Marini F, Andreeff M, Sorrentino BP. Low levels of ABCG2 expression in adult AML blast samples. Blood. 2002;100:4594–4601. doi: 10.1182/blood-2002-01-0271. [PubMed] [Cross Ref]
109. Kolk DM, Vellenga E, Scheffer GL, et al. Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia. Blood. 2002;99:3763–3770. doi: 10.1182/blood.V99.10.3763. [PubMed] [Cross Ref]
110. Sauerbrey A, Sell W, Steinbach D, Voigt A, Zintl F. Expression of the BCRP gene (ABCG2/MXR/ABCP) in childhood acute lymphoblastic leukaemia. Br J Haematol. 2002;118:147–150. doi: 10.1046/j.1365-2141.2002.03550.x. [PubMed] [Cross Ref]
111. Plasschaert SL, Kolk DM, Bont ES, et al. The role of breast cancer resistance protein in acute lymphoblastic leukemia. Clin Cancer Res. 2003;9:5171–5177. [PubMed]
112. Ren JH, Du XY, Guo XN, et al. Relationship between resistance to chemotherapy and expression of breast cancer resistance protein (BCRP) gene in patients with acute leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2004;12:55–58. [PubMed]
113. Pol MA, Broxterman HJ, Pater JM, et al. Function of the ABC transporters. P-glycoprotein, multidrug resistance protein and breast cancer resistance protein, in minimal residual disease in acute myeloid leukemia. Haematologica. 2003;88:134–147. [PubMed]
114. Heuvel-Eibrink MM, Wiemer EA, Prins A, et al. Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML) Leukemia. 2002;16:833–839. doi: 10.1038/sj.leu.2402496. [PubMed] [Cross Ref]
115. Sargent JM, Williamson CJ, Maliepaard M, Elgic AW, Scheper RJ, Taylor CG. Breast cancer resistance protein expression and resistance to daunorubicin in blast cells from patients with acute myeloid leukaemia. Br J Haematol. 2001;115:257–262. doi: 10.1046/j.1365-2141.2001.03122.x. [PubMed] [Cross Ref]
116. Stam RW, Heuvel-Eibrink MM, Boer ML, et al. Multidrug resistance genes in infant acute lymphoblastic leukemia: Ara-C is not a substrate for the breast cancer resistance protein. Leukemia. 2004;18:78–83. doi: 10.1038/sj.leu.2403168. [PubMed] [Cross Ref]
117. Suvannasankha A, Minderman H, O'Loughlin KL, et al. Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function. Leukemia. 2004;18:1252–1257. doi: 10.1038/sj.leu.2403395. [PubMed] [Cross Ref]
118. Scheffer GL, Maliepaard M, Pijnenborg AC, et al. Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone-and topotecan-resistant cell lines. Cancer Res. 2000;60:2589–2593. [PubMed]
119. Diestra JE, Scheffer GL, Catala I, et al. Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material. J Pathol. 2002;198:213–219. doi: 10.1002/path.1203. [PubMed] [Cross Ref]
120. Kawabata S, Oka M, Soda H, et al. Expression and functional analyses of breast cancer resistance protein in lung cancer. Clin Cancer Res. 2003;9:3052–3057. [PubMed]
121. Yoh K, Ishii G, Yokose T, et al. Breast cancer resistance protein impacts clinical outcome in platinum-based chemotherapy for advanced non-small cell lung cancer. Clin Cancer Res. 2004;10:1691–1697. doi: 10.1158/1078-0432.CCR-0937-3. [PubMed] [Cross Ref]
122. Candeil L, Gourdier I, Peyron D, et al. ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases. Int J Cancer. 2004;109:848–854. doi: 10.1002/ijc.20032. [PubMed] [Cross Ref]
123. Kanzaki A, Toi M, Nakayama K, et al. Expression of multidrug resistance-related transporters in human breast carcinoma. Jpn J Cancer Res. 2001;92:452–458. [PubMed]
124. Faneyte IF, Kristel PM, Maliepaard M, et al. Expression of the breast cancer resistance protein in breast cancer. Clin Cancer Res. 2002;8:1068–1074. [PubMed]
125. Burger H, Foekens JA, Look MP, et al. RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response. Clin Cancer Res. 2003;9:827–836. [PubMed]
126. Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP. Berp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci USA. 2002;99:12339–12344. doi: 10.1073/pnas.192276999. [PMC free article] [PubMed] [Cross Ref]
127. Tamaki T, Akatsuka A, Ando K, et al. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol. 2002;157:571–577. doi: 10.1083/jcb.200112106. [PMC free article] [PubMed] [Cross Ref]
128. Leehner A, Leech CA, Abraham EJ, Nolan AL, Habener JF. Nestinpositive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter. Biochem Biophys Res Commun. 2002;293:670–674. doi: 10.1016/S0006-291X(02)00275-9. [PubMed] [Cross Ref]
129. Shimano K, Satake M, Okaya A, et al. Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1. Am J Pathol. 2003;163:3–9. [PMC free article] [PubMed]
130. Martin CM, Meeson AP, Robertson SM, et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol. 2004;265:262–275. doi: 10.1016/j.ydbio.2003.09.028. [PubMed] [Cross Ref]
131. Krishnamurthy P, Ross DD, Nakanishi T, et al. The stem cell marker Berp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem. 2004;279:24218–24225. doi: 10.1074/jbc.M313599200. [PubMed] [Cross Ref]
132. Sarkadi B, Ozvegy-Laczka C, Nemet K, Varadi A. ABCG2-a transporter for all seasons. FEBS Lett. 2004;567:116–120. doi: 10.1016/j.febslet.2004.03.123. [PubMed] [Cross Ref]
133. Bunting KD. ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells. 2002;20:11–20. doi: 10.1634/stemcells.20-3-274. [PubMed] [Cross Ref]
134. Abbott BL. ABCG2 (BCRP) expression in normal and malignant hematopoietic cells. Hematol Oncol. 2003;21:115–130. doi: 10.1002/hon.714. [PubMed] [Cross Ref]
135. Taipalensuu J, Tornblom H, Lindberg G, et al. Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther. 2001;299:164–170. [PubMed]
136. Cooray HC, Blackmore CG, Maskell L, Barrand MA. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport. 2002;13:2059–2063. doi: 10.1097/00001756-200211150-00014. [PubMed] [Cross Ref]
137. Zhang W, Mojsilovic-Petrovic J, Andrade MF, Zhang H, Ball M, Stanimirovic DB. The expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J. 2003;17:2085–2087. [PubMed]
138. Troger U, Stotzel B, Martens-Lobenhoffer J, Gollnick H, Meyer FP. Drug points: severe myalgia from an interaction between treatments with pantoprazole and methotrexate. BMJ. 2002;324:1497–1497. doi: 10.1136/bmj.324.7352.1497. [PMC free article] [PubMed] [Cross Ref]
139. Mizuno N, Suzuki M, Kusuhara H, et al. Impaired renal excretion of 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) sulfate in breast cancer resistance protein (BCRP1/ABCG2) knockout mice. Drug Metab Dispos. 2004;32:898–901. [PubMed]
140. Cisternino S, Mercier C, Bourasset F, Roux F, Scherrmann JM. Expression, up-regulation, and transport activity of the multidrug-resistance protein abcg2 at the mouse blood-brain barrier. Cancer Res. 2004;64:3296–3301. doi: 10.1158/0008-5472.CAN-03-2033. [PubMed] [Cross Ref]

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