Ins and outs of the ABCG2 multidrug transporter: An update on in vitro functional assays

Advanced Drug Delivery Reviews

Volumn 61, Issue 1, 2009, Pages 47-56

  Hegedus, Csilla ^a   Szakács, Gergely ^b   Homolya, László ^a   Orbán, Tamás I ^a   Telbisz, Ágnes ^a   Jani, Márton ^c   Sarkadi, Balázs ^a  

^a SEMMELWEIS UNIVERSITY   (Hungary)

^b INSTITUTE OF ENZYMOLOGY   (Hungary)

^c SOLVO BIOTECHNOLOGY   (Hungary)

Author keywords

ABCG2; ADME Tox; Cellular assays; Conformation sensitive antibody; Fluorescent proteins; Membrane based assays; Multidrug resistance

Indexed keywords

ABCG2; ADME-TOX; CELLULAR ASSAYS; CONFORMATION SENSITIVE ANTIBODY; FLUORESCENT PROTEINS; MEMBRANE-BASED ASSAYS; MULTIDRUG RESISTANCE;

ANTIBODIES; CELL MEMBRANES; DRUG INTERACTIONS; FLUORESCENCE; PROTEINS;

ASSAYS;

7 ETHYL 10 HYDROXYCAMPTOTHECIN; ADENOSINE TRIPHOSPHATASE; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; BREAST CANCER RESISTANCE PROTEIN; CHOLESTEROL; DACTINOMYCIN; DOXORUBICIN; DRUG METABOLITE; FLAVOPIRIDOL; FLUORESCENT DYE; GEFITINIB; GREEN FLUORESCENT PROTEIN; HOE 33342; HYBRID PROTEIN; IMATINIB; LUCIFER YELLOW; MEMBRANE LIPID; METHOTREXATE; MITOXANTRONE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY MRK 16; PLASTIC; PRAZOSIN; PROTEIN KINASE INHIBITOR; SALAZOSULFAPYRIDINE; TOPOTECAN; UNINDEXED DRUG; VINCRISTINE; XENOBIOTIC AGENT;

BIOASSAY; CYTOTOXICITY; DRUG CYTOTOXICITY; DRUG PROTEIN BINDING; DRUG TRANSPORT; ENZYME ACTIVITY; FLOW CYTOMETRY; HUMAN; HYDROPHOBICITY; MEMBRANE VESICLE; MONOLAYER CULTURE; NONHUMAN; PHOTOAFFINITY LABELING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SYNTHESIS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

ATP-BINDING CASSETTE TRANSPORTERS; BIOLOGICAL ASSAY; DRUG INTERACTIONS; DRUG RESISTANCE, MULTIPLE; HUMANS; NEOPLASM PROTEINS; SUBSTRATE SPECIFICITY;

EID: 59049096478     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2008.09.007     Document Type: Review

References (118)

1. Dean M., Fojo T., and Bates S. Tumour stem cells and drug resistance. Nat. Rev., Cancer 5 (2005) 275-284
2. Sarkadi B., Homolya L., Szakacs G., and Varadi A. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol. Rev. 86 (2006) 1179-1236
3. Krishnamurthy P., and Schuetz J.D. Role of ABCG2/BCRP in biology and medicine. Annu. Rev. Pharmacol. Toxicol. 46 (2006) 381-410
4. Szakacs G., Paterson J.K., Ludwig J.A., Booth-Genthe C., and Gottesman M.M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 5 (2006) 219-234
5. Szakacs G., Varadi A., Ozvegy-Laczka C., and Sarkadi B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov. Today 13 (2008) 379-393
6. Maliepaard M., Scheffer G.L., Faneyte I.F., van Gastelen M.A., Pijnenborg A.C., Schinkel A.H., van De Vijver M.J., Scheper R.J., and Schellens J.H. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 61 (2001) 3458-3464
7. Zhou S., Schuetz J.D., Bunting K.D., Colapietro A.M., Sampath J., Morris J.J., Lagutina I., Grosveld G.C., Osawa M., Nakauchi H., and Sorrentino B.P. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med. 7 (2001) 1028-1034
8. Sarkadi B., Ozvegy-Laczka C., Nemet K., and Varadi A. ABCG2 - a transporter for all seasons. FEBS Lett. 567 (2004) 116-120
9. Cervenak J., Andrikovics H., Ozvegy-Laczka C., Tordai A., Nemet K., Varadi A., and Sarkadi B. The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology. Cancer Lett. 234 (2006) 62-72
10. Allen J.D., van Loevezijn A., Lakhai J.M., van der Valk M., van Tellingen O., Reid G., Schellens J.H., Koomen G.J., and Schinkel A.H. 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 (2002) 417-425
11. Ozvegy C., Varadi A., and 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. 277 (2002) 47980-47990
12. Litman T., Jensen U., Hansen A., Covitz K.M., Zhan Z., Fetsch P., Abati A., Hansen P.R., Horn T., Skovsgaard T., and Bates S.E. Use of peptide antibodies to probe for the mitoxantrone resistance-associated protein MXR/BCRP/ABCP/ABCG2. Biochim. Biophys. Acta 1565 (2002) 6-16
13. Diop N.K., and Hrycyna C.A. N-Linked glycosylation of the human ABC transporter ABCG2 on asparagine 596 is not essential for expression, transport activity, or trafficking to the plasma membrane. Biochemistry 44 (2005) 5420-5429
14. Takada T., Suzuki H., and Sugiyama Y. Characterization of polarized expression of point- or deletion-mutated human BCRP/ABCG2 in LLC-PK1 cells. Pharmacol. Res. 22 (2005) 458-464
15. Mohrmann K., van Eijndhoven M.A., Schinkel A.H., and Schellens J.H. Absence of N-linked glycosylation does not affect plasma membrane localization of breast cancer resistance protein (BCRP/ABCG2). Cancer Chemother. Pharmacol. 56 (2005) 344-350
16. Kage K., Fujita T., and Sugimoto Y. Role of Cys-603 in dimer/oligomer formation of the breast cancer resistance protein BCRP/ABCG2. Cancer Sci. 96 (2005) 866-872
17. Henriksen U., Fog J.U., Litman T., and Gether U. Identification of intra- and intermolecular disulfide bridges in the multidrug resistance transporter ABCG2. J. Biol. Chem. 280 (2005) 36926-36934
18. Wakabayashi K., Nakagawa H., Adachi T., Kii I., Kobatake E., Kudo A., and Ishikawa T. Identification of cysteine residues critically involved in homodimer formation and protein expression of human ATP-binding cassette transporter ABCG2: a new approach using the flp recombinase system. J. Exp. Ther. Oncol. 5 (2006) 205-222
19. Honjo Y., Hrycyna C.A., Yan Q.W., Medina-Perez W.Y., Robey R.W., van de Laar A., Litman T., Dean M., and Bates S.E. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res. 61 (2001) 6635-6639
20. Volk E.L., Farley K.M., Wu Y., Li F., Robey R.W., and Schneider E. Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance. Cancer Res. 62 (2002) 5035-5040
21. Chen Z.S., Robey R.W., Belinsky M.G., Shchaveleva I., Ren X.Q., Sugimoto Y., Ross D.D., Bates S.E., and Kruh G.D. 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. 63 (2003) 4048-4054
22. Mitomo H., Kato R., Ito A., Kasamatsu S., Ikegami Y., Kii I., Kudo A., Kobatake E., Sumino Y., and Ishikawa T. A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem. J. 373 (2003) 767-774
23. Ozvegy-Laczka C., Koblos G., Sarkadi B., and Varadi A. Single amino acid (482) variants of the ABCG2 multidrug transporter: major differences in transport capacity and substrate recognition. Biochim. Biophys. Acta 1668 (2005) 53-63
24. Robey R.W., Honjo Y., Morisaki K., Nadjem T.A., Runge S., Risbood M., Poruchynsky M.S., and Bates S.E. Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br. J. Cancer 89 (2003) 1971-1978
25. Miwa M., Tsukahara S., Ishikawa E., Asada S., Imai Y., and 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 107 (2003) 757-763
26. Ejendal K.F., Diop N.K., Schweiger L.C., and Hrycyna C.A. The nature of amino acid 482 of human ABCG2 affects substrate transport and ATP hydrolysis but not substrate binding. Protein Sci. 15 (2006) 1597-1607
27. Tamura A., Watanabe M., Saito H., Nakagawa H., Kamachi T., Okura I., and Ishikawa T. 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 (2006) 287-296
28. Tamura A., Wakabayashi K., Onishi Y., Takeda M., Ikegami Y., Sawada S., Tsuji M., Matsuda Y., and Ishikawa T. Re-evaluation and functional classification of non-synonymous single nucleotide polymorphisms of the human ATP-binding cassette transporter ABCG2. Cancer Sci. 98 (2007) 231-239
29. Jonker J.W., Buitelaar M., Wagenaar E., Van Der Valk M.A., Scheffer G.L., Scheper R.J., Plosch T., Kuipers F., Elferink R.P., Rosing H., Beijnen J.H., and Schinkel A.H. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 15649-15654
30. Zhou S., Morris J.J., Barnes Y., Lan L., Schuetz J.D., and Sorrentino B.P. Bcrp1 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. U. S. A. 99 (2002) 12339-12344
31. Chandra P., and Brouwer K.L. The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm. Res. 21 (2004) 719-735
32. Mizuno N., Niwa T., Yotsumoto Y., and Sugiyama Y. Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. 55 (2003) 425-461
33. Sharom F.J., Yu X., Lu P., Liu R., Chu J.W., Szabo K., Muller M., Hose C.D., Monks A., Varadi A., Seprodi J., and Sarkadi B. Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells. Biochem. Pharmacol. 58 (1999) 571-586
34. Glavinas H., Krajcsi P., Cserepes J., and Sarkadi B. The role of ABC transporters in drug resistance, metabolism and toxicity. Curr. Drug Deliv. 1 (2004) 27-42
35. Pavek P., Merino G., Wagenaar E., Bolscher E., Novotna M., Jonker J.W., and Schinkel A.H. 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 (2005) 144-152
36. Ozvegy C., Litman T., Szakacs G., Nagy Z., Bates S., Varadi A., and Sarkadi B. Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem. Biophys. Res. Commun. 285 (2001) 111-117
37. Volk E.L., Rohde K., Rhee M., McGuire J.J., Doyle L.A., Ross D.D., and Schneider E. Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux. Cancer Res. 60 (2000) 3514-3521
38. Kuchler K., and Thorner J. Functional expression of human mdr1 in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U. S. A. 89 (1992) 2302-2306
39. Pal A., Mehn D., Molnar E., Gedey S., Meszaros P., Nagy T., Glavinas H., Janaky T., von Richter O., Bathori G., Szente L., and Krajcsi P. Cholesterol potentiates ABCG2 activity in a heterologous expression system: improved in vitro model to study function of human ABCG2. J. Pharmacol. Exp. Ther. 321 (2007) 1085-1094
40. Steck T.L., Weinstein R.S., Straus J.H., and Wallach D.F. Inside-out red cell membrane vesicles: preparation and purification. Science 168 (1970) 255-257
41. Steck T.L., and Kant J.A. Preparation of impermeable ghosts and inside-out vesicles from human erythrocyte membranes. Methods Enzymol. 31 (1974) 172-180
42. Ochs D.L., and Reed P.W. ATP-dependent calcium transport in plasma membrane vesicles from neutrophil leukocytes. J. Biol. Chem. 258 (1983) 10116-10122
43. Ambudkar S.V., Lelong I.H., Zhang J., and Cardarelli C. Purification and reconstitution of human P-glycoprotein. Methods Enzymol. 292 (1998) 492-504
44. Doige C.A., and Sharom F.J. Transport properties of P-glycoprotein in plasma membrane vesicles from multidrug-resistant Chinese hamster ovary cells. Biochim. Biophys. Acta 1109 (1992) 161-171
45. Broxterman H.J., Pinedo H.M., Kuiper C.M., Kaptein L.C., Schuurhuis G.J., and Lankelma J. Induction by verapamil of a rapid increase in ATP consumption in multidrug-resistant tumor cells. FASEB J. 2 (1988) 2278-2282
46. Sarkadi B., Price E.M., Boucher R.C., Germann U.A., and Scarborough G.A. Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J. Biol. Chem. 267 (1992) 4854-4858
47. Doige C.A., Yu X., and Sharom F.J. ATPase activity of partially purified P-glycoprotein from multidrug-resistant Chinese hamster ovary cells. Biochim. Biophys. Acta 1109 (1992) 149-160
48. Ambudkar S.V., Lelong I.H., Zhang J., Cardarelli C.O., Gottesman M.M., and Pastan I. Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc. Natl. Acad. Sci. U. S. A. 89 (1992) 8472-8476
49. Horio M., Gottesman M.M., and Pastan I. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proc. Natl. Acad. Sci. U. S. A. 85 (1988) 3580-3584
50. Breedveld P., Pluim D., Cipriani G., Dahlhaus F., van Eijndhoven M.A., de Wolf C.J., Kuil A., Beijnen J.H., Scheffer G.L., Jansen G., Borst P., and Schellens J.H. The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol. Pharmacol. 71 (2007) 240-249
51. Saito H., Hirano H., Nakagawa H., Fukami T., Oosumi K., Murakami K., Kimura H., Kouchi T., Konomi M., Tao E., Tsujikawa N., Tarui S., Nagakura M., Osumi M., and Ishikawa T. A new strategy of high-speed screening and quantitative structure-activity relationship analysis to evaluate human ATP-binding cassette transporter ABCG2drug interactions. J. Pharmacol. Exp. Ther. 317 (2006) 1114-1124
52. Shukla S., Robey R.W., Bates S.E., and Ambudkar S.V. The calcium channel blockers, 1,4dihydropyridines, are substrates of the multidrug resistance-linked ABC drug transporter, ABCG2. Biochemistry 45 (2006) 8940-8951
53. Chearwae W., Shukla S., Limtrakul P., and Ambudkar S.V. Modulation of the function of the multidrug resistance-linked ATP-binding cassette transporter ABCG2 by the cancer chemopreventive agent curcumin. Mol. Cancer Ther. 5 (2006) 1995-2006
54. Limtrakul P., Chearwae W., Shukla S., Phisalphong C., and Ambudkar S.V. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin. Mol. Cell. Biochem. 296 (2007) 85-95
55. Robey R.W., Shukla S., Steadman K., Obrzut T., Finley E.M., Ambudkar S.V., and Bates S.E. Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure. Mol. Cancer Ther. 6 (2007) 1877-1885
56. Shi Z., Peng X.X., Kim I.W., Shukla S., Si Q.S., Robey R.W., Bates S.E., Shen T., Ashby Jr. C.R., Fu L.W., Ambudkar S.V., and Chen Z.S. Erlotinib (Tarceva, OSI-774) antagonizes ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance. Cancer Res. 67 (2007) 11012-11020
57. Shukla S., Wu C.P., Nandigama K., and Ambudkar S.V. 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 (2007) 3279-3286
58. Henrich C.J., Robey R.W., Bokesch H.R., Bates S.E., Shukla S., Ambudkar S.V., Dean M., and McMahon J.B. New inhibitors of ABCG2 identified by high-throughput screening. Mol. Cancer Ther. 6 (2007) 3271-3278
59. Wu C.P., Shukla S., Calcagno A.M., Hall M.D., Gottesman M.M., and Ambudkar S.V. Evidence for dual mode of action of a thiosemicarbazone, NSC73306: a potent substrate of the multidrug resistance linked ABCG2 transporter. Mol. Cancer Ther. 6 (2007) 3287-3296
60. Shukla S., Sauna Z.E., and Ambudkar S.V. Evidence for the interaction of imatinib at the transport-substrate site(s) of the multidrug-resistance-linked ABC drug transporters ABCB1 (P-glycoprotein) and ABCG2. Leukemia 22 (2008) 445-447
61. al-Shawi M.K., Urbatsch I.L., and Senior A.E. Covalent inhibitors of P-glycoprotein ATPase activity. J. Biol. Chem. 269 (1994) 8986-8992
62. Urbatsch I.L., Sankaran B., Weber J., and Senior A.E. P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J. Biol. Chem. 270 (1995) 19383-19390
63. Senior A.E., and Gadsby D.C. ATP hydrolysis cycles and mechanism in P-glycoprotein and CFTR. Semin. Cancer Biol. 8 (1997) 143-150
64. Szabo K., Welker E., Bakos, Muller M., Roninson I., Varadi A., and Sarkadi B. Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1. Cooperation of the nucleotide binding domains. J. Biol. Chem. 273 (1998) 10132-10138
65. Elkind N.B., Szentpetery Z., Apati A., Ozvegy-Laczka C., Varady G., Ujhelly O., Szabo K., Homolya L., Varadi A., Buday L., Keri G., Nemet K., and Sarkadi B. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib). Cancer Res. 65 (2005) 1770-1777
66. Nakanishi T., Shiozawa K., Hassel B.A., and Ross D.D. Complex interaction of BCRP/ABCG2 and imatinib in BCR-ABL-expressing cells: BCRP-mediated resistance to imatinib is attenuated by imatinib-induced reduction of BCRP expression. Blood 108 (2006) 678-684
67. Brendel C., Scharenberg C., Dohse M., Robey R.W., Bates S.E., Shukla S., Ambudkar S.V., Wang Y., Wennemuth G., Burchert A., Boudriot U., and Neubauer A. Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia 21 (2007) 1267-1275
68. Meunier V., Bourrie M., Berger Y., and Fabre G. The human intestinal epithelial cell line Caco-2; pharmacological and pharmacokinetic applications. Cell Biol. Toxicol. 11 (1995) 187-194
69. van Breemen R.B., and Li Y. Caco-2 cell permeability assays to measure drug absorption. Expert Opin. Drug Metab. Toxicol. 1 (2005) 175-185
70. Schlatter P., Gutmann H., and Drewe J. Primary porcine proximal tubular cells as a model for transepithelial drug transport in human kidney. Eur. J. Pharm. Sci. 28 (2006) 141-154
71. Liang E., Proudfoot J., and Yazdanian M. Mechanisms of transport and structure-permeability relationship of sulfasalazine and its analogs in Caco-2 cell monolayers. Pharm. Res. 17 (2000) 1168-1174
72. Sun H., and Pang K.S. Permeability, transport, and metabolism of solutes in Caco-2 cell monolayers: a theoretical study. Drug Metab. Dispos. 36 (2008) 102-123
73. Jonker J.W., Smit J.W., Brinkhuis R.F., Maliepaard M., Beijnen J.H., Schellens J.H., and Schinkel A.H. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J. Natl. Cancer Inst. 92 (2000) 1651-1656
74. Merino G., Jonker J.W., Wagenaar E., Pulido M.M., Molina A.J., Alvarez A.I., and Schinkel A.H. Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2). Drug Metab. Dispos. 33 (2005) 614-618
75. Taub M.E., Podila L., Ely D., and Almeida I. Functional assessment of multiple Pglycoprotein (P-gp) probe substrates: influence of cell line and modulator concentration on P-gp activity. Drug Metab. Dispos. 33 (2005) 1679-1687
76. Nies A.T., Schwab M., and Keppler D. Interplay of conjugating enzymes with OATP uptake transporters and ABCC/MRP efflux pumps in the elimination of drugs. Expert Opin. Drug Metab. Toxicol. 4 (2008) 545-568
77. Xia C.Q., Liu N., Yang D., Miwa G., and Gan L.S. Expression, localization, and functional characteristics of breast cancer resistance protein in Caco-2 cells. Drug Metab. Dispos. 33 (2005) 637-643
78. Siissalo S., Laitinen L., Koljonen M., Vellonen K.S., Kortejarvi H., Urtti A., Hirvonen J., and Kaukonen A.M. Effect of cell differentiation and passage number on the expression of efflux proteins in wild type and vinblastine-induced Caco-2 cell lines. Eur. J. Pharm. Biopharm. 67 (2007) 548-554
79. Ebert B., Seidel A., and Lampen A. Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists. Carcinogenesis 26 (2005) 1754-1763
80. Lemos C., Kathmann I., Giovannetti E., Dekker H., Scheffer G.L., Calhau C., Jansen G., and Peters G.J. Folate deprivation induces BCRP (ABCG2) expression and mitoxantrone resistance in Caco-2 cells. Int. J. Cancer 123 (2008) 1712-1720
81. W. Brand, P.A. van derWel, M.J. Rein, D. Barron, G.Williamson, P.J. van Bladeren, I.M. Rietjens, Metabolismand transport of the citrus flavonoid hesperetin in Caco-2 cell monolayers, Drug Metab. Dispos. 2008 Sep;36(9):1794-1802.
82. Hamada H., and Tsuruo T. Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies. Proc. Natl. Acad. Sci. U. S. A. 83 (1986) 7785-7789
83. Meyers M.B., Rittmann-Grauer L., O'Brien J.P., and Safa A.R. Characterization of monoclonal antibodies recognizing a Mr 180,000 P-glycoprotein: differential expression of the Mr 180,000 and Mr 170,000 P-glycoproteins in multidrug-resistant human tumor cells. Cancer Res. 49 (1989) 3209-3214
84. Cenciarelli C., Currier S.J., Willingham M.C., Thiebaut F., Germann U.A., Rutherford A.V., Gottesman M.M., Barca S., Tombesi M., Morrone S., Santoni A., Mariani M., Ramoni C., Dupuis M.L., and Cianfriglia M. Characterization by somatic cell genetics of a monoclonal antibody to the MDR1 gene product (P-glycoprotein): determination of P-glycoprotein expression in multi-drug-resistant KB and CEM cell variants. Int. J. Cancer 47 (1991) 533-543
85. Mechetner E.B., and Roninson I.B. Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc. Natl. Acad. Sci. U. S. A. 89 (1992) 5824-5828
86. Tsuruo T., Hamada H., Sato S., and Heike Y. Inhibition of multidrug-resistant human tumor growth in athymic mice by anti-P-glycoprotein monoclonal antibodies. Jpn. J. Cancer Res. 80 (1989) 627-631
87. Hamada H., Miura K., Ariyoshi K., Heike Y., Sato S., Kameyama K., Kurosawa Y., and Tsuruo T. Mouse-human chimeric antibody against the multidrug transporter Pglycoprotein. Cancer Res. 50 (1990) 3167-3171
88. Iwahashi T., Okochi E., Ariyoshi K., Watabe H., Amann E., Mori S., Tsuruo T., and Ono K. Specific targeting and killing activities of anti-P-glycoprotein monoclonal antibody MRK16 directed against intrinsically multidrug-resistant human colorectal carcinoma cell lines in the nude mouse model. Cancer Res. 53 (1993) 5475-5482
89. Mechetner E.B., Schott B., Morse B.S., Stein W.D., Druley T., Davis K.A., Tsuruo T., and Roninson I.B. P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity. Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 12908-12913
90. Abbott B.L., Colapietro A.M., Barnes Y., Marini F., Andreeff M., and Sorrentino B.P. Low levels of ABCG2 expression in adult AML blast samples. Blood 100 (2002) 4594-4601
91. Ozvegy-Laczka C., Varady G., Koblos G., Ujhelly O., Cervenak J., Schuetz J.D., Sorrentino B.P., Koomen G.J., Varadi A., Nemet K., and Sarkadi B. Function-dependent conformational changes of the ABCG2 multidrug transporter modify its interaction with a monoclonal antibody on the cell surface. J. Biol. Chem. 280 (2005) 4219-4227
92. C. Ozvegy-Laczka, R. Laczkó, C. Hegedus, T. Litman, G. Várady, K. Goda, T. Hegedus, N.V. Dokholyan, B.P. Sorrentino, A. Váradi, B. Sarkadi, Interaction with the 5D3 monoclonal antibody is regulated by intramolecular rearrangements but not by covalent dimer formation of the human ABCG2 multidrug transporter, J. Biol. Chem. 2008 Sep 19;283(38):26059-26070.
93. Hollo Z., Homolya L., Davis C.W., and Sarkadi B. Calcein accumulation as a fluorometric functional assay of the multidrug transporter. Biochim. Biophys. Acta 1191 (1994) 384-388
94. Karaszi E., Jakab K., Homolya L., Szakacs G., Hollo Z., Telek B., Kiss A., Rejto L., Nahajevszky S., Sarkadi B., and Kappelmayer J. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br. J. Haematol. 112 (2001) 308-314
95. Ivnitski-Steele I., Larson R.S., Lovato D.M., Khawaja H.M., Winter S.S., Oprea T.I., Sklar L.A., and Edwards B.S. High-throughput flow cytometry to detect selective inhibitors of ABCB1, ABCC1, and ABCG2 transporters. Assay Drug Dev. Technol. 6 (2008) 263-276
96. Robey R.W., Steadman K., Polgar O., Morisaki K., Blayney M., Mistry P., and Bates S.E. Pheophorbide a is a specific probe for ABCG2 function and inhibition. Cancer Res. 64 (2004) 1242-1246
97. Henrich C.J., Bokesch H.R., Dean M., Bates S.E., Robey R.W., Goncharova E.I., Wilson J.A., and McMahon J.B. A high-throughput cell-based assay for inhibitors of ABCG2 activity. J. Biomol. Screen. 11 (2006) 176-183
98. Robey R.W., Steadman K., Polgar O., and Bates S.E. ABCG2-mediated transport of photosensitizers: potential impact on photodynamic therapy. Cancer Biol. Ther. 4 (2005) 187-194
99. Hirschmann-Jax C., Foster A.E., Wulf G.G., Nuchtern J.G., Jax T.W., Gobel U., Goodell M.A., and Brenner M.K. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 14228-14233
100. Scharenberg C.W., Harkey M.A., and Torok-Storb B. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99 (2002) 507-512
101. Petriz J., Gottesman M.M., and Aran J.M. An MDR-EGFP gene fusion allows for direct cellular localization, function and stability assessment of P-glycoprotein. Curr. Drug Deliv. 1 (2004) 43-56
102. Orban T.I., Seres L., Ozvegy-Laczka C., Elkind N.B., Sarkadi B., and Homolya L. Combined localization and real-time functional studies using a GFP-tagged ABCG2 multidrug transporter. Biochem. Biophys. Res. Commun. 367 (2008) 667-673
103. Schroeder K.S., and Neagle B.D. FLIPR: A New Instrument for Accurate, High Throughput Optical Screening. J. Biomol. Screen. 1 2 (1996) 75-80
104. Orlowski S., Comera C., Terce F., and Collet X. Lipid rafts: dream or reality for cholesterol transporters?. Eur. Biophys. J. 36 (2007) 869-885
105. Radeva G., Perabo J., and Sharom F.J. P-Glycoprotein is localized in intermediate-density membrane microdomains distinct from classical lipid rafts and caveolar domains. FEBS J. 272 (2005) 4924-4937
106. Fenyvesi F., Fenyvesi E., Szente L., Goda K., Bacso Z., Bacskay I., Varadi J., Kiss T., Molnar E., Janaky T., Szabo Jr. G., and Vecsernyes M. P-glycoprotein inhibition by membrane cholesterol modulation. Eur. J. Pharm. Sci. 34 (2008) 236-242
107. Dos Santos S.M., Weber C.C., Franke C., Muller W.E., and Eckert G.P. Cholesterol: Coupling between membrane microenvironment and ABC transporter activity. Biochem. Biophys. Res. Commun. 354 (2007) 216-221
108. Storch C.H., Ehehalt R., Haefeli W.E., and Weiss J. Localization of the human breast cancer resistance protein (BCRP/ABCG2) in lipid rafts/caveolae and modulation of its activity by cholesterol in vitro. J. Pharmacol. Exp. Ther. 323 (2007) 257-264
109. Telbisz A., Muller M., Ozvegy-Laczka C., Homolya L., Szente L., Varadi A., and Sarkadi B. Membrane cholesterol selectively modulates the activity of the human ABCG2 multidrug transporter. Biochim. Biophys. Acta 1768 (2007) 2698-2713
110. Suzuki M., Suzuki H., Sugimoto Y., and Sugiyama Y. ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem 278 (2003) 22644-22649
111. Imai Y., Asada S., Tsukahara S., Ishikawa E., Tsuruo T., and Sugimoto Y. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol. Pharmacol. 64 (2003) 610-618
112. Janvilisri T., Venter H., Shahi S., Reuter G., Balakrishnan L., and van Veen H.W. Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J. Biol. Chem. 278 (2003) 20645-20651
113. Janvilisri T., Shahi S., Venter H., Balakrishnan L., and 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. 385 (2005) 419-426
114. Velamakanni S., Janvilisri T., Shahi S., and van Veen H.W. A functional steroid-binding element in an ATP-binding cassette multidrug transporter. Mol. Pharmacol. 73 (2008) 12-17
115. Gimpl G., Klein U., Reilander H., and Fahrenholz F. Expression of the human oxytocin receptor in baculovirus-infected insect cells: high-affinity binding is induced by a cholesterol-cyclodextrin complex. Biochemistry 34 (1995) 13794-13801
116. Marheineke K., Grunewald S., Christie W., and Reilander H. Lipid composition of Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tn) insect cells used for baculovirus infection. FEBS Lett. 441 (1998) 49-52
117. Burger K., Gimpl G., and Fahrenholz F. Regulation of receptor function by cholesterol. Cell. Mol. Life Sci. 57 (2000) 1577-1592
118. Zidovetzki R., and Levitan I. Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies. Biochim. Biophys. Acta 1768 (2007) 1311-1324