| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Divisions of Experimental Therapy [J. D. A., R. F. B., A. H. S.] and Molecular Biology [J. W.], The Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands
| ABSTRACT |
|---|
|
|
|---|
| Introduction |
|---|
|
|
|---|
Mouse cell lines lacking functional Mdr1a and Mdr1b (encoding mouse P-gps), and Mrp1 genes constitute a potentially fertile resource for identifying new mechanisms of drug resistance. Such lines are markedly more sensitive than equivalent wild-type lines are to P-gp and MRP1 substrate drugs, including doxorubicin, paclitaxel, topotecan, and vincristine.4 Selection of these lines for resistance to antineoplastic drugs may, therefore, invoke resistance mechanisms normally masked or overshadowed by the presence of P-gp or Mrp1. Indeed, we report here that selection with topotecan, mitoxantrone, or doxorubicin readily resulted in overexpression of the mouse Bcrp1 gene.
| Materials and Methods |
|---|
|
|
|---|
Drug Resistance Assays.
Growth inhibition (IC50) assays were performed by seeding 250 or 500 cells per well in 96-well plates in complete medium and applying drugs in a dilution series, each concentration in quadruplicate wells. After 44.5 days, when unselected wells were still subconfluent, cells were lysed in situ, nucleic acids were stained with a proprietary dye (Cyquant, Molecular Probes, Eugene, OR), and quantified by UV fluorescence (485 nm excitation, 530 nm emission). All such assays were performed three times.
Mitoxantrone Accumulation and Efflux Assays.
Relative cellular accumulation of mitoxantrone was determined by flow cytometry using excitation at 633 nm and a 661 nm band-pass filter to detect emission. All of the assays were conducted at 37°C with 105 (subconfluent) cells per well in 12-well plates, seeded in complete medium without drug the night before. Mitoxantrone was added for timed intervals in fresh, prewarmed, complete medium containing 5% FCS. Accumulation or efflux was arrested by prompt cooling on ice, and the cells were maintained at 0°C during all of the subsequent steps, including trypsinizing. Where indicated (see "Results"), mitoxantrone accumulations were done in the presence of 2 µM GF120918; pilot experiments indicated that this concentration gave >95% maximal effect. Cells were preincubated with GF120918 for 3060 min before adding mitoxantrone. Accumulation under ATP-depleting conditions was performed for 2 h in glucose-free, pyruvate-free DMEM containing 5% dialyzed FCS, plus 10 mM sodium azide to inhibit oxidative phosphorylation, as described previously (19)
. Mitoxantrone efflux was assayed after accumulation under ATP-depleting conditions: the medium and drug were removed by aspiration, wells were washed quickly with complete medium at room temperature, and the cells were then incubated with prewarmed complete medium at 37°C for timed intervals prior to harvesting. Assays were performed at least twice, each time with triplicate wells.
Bcrp Cloning and Sequencing.
Mouse Bcrp1 cDNAs were amplified by PCR with primers based on mouse EST sequences homologous to the 5' and 3' ends of human BCRP, with XbaI linkers added: 5'-GAG TGA GAT CTA GAA GGC ATA AAT CCT AAA GAT GTC TTC C and 3'-AAG GTA AGT CTA GAG GAG TAC AAT TAA TAG TCC GTT AAA GG. The PCR was performed with Pfu polymerase, Stratagene, La Jolla, CA) on oligo-dT primed first-strand cDNA from liver, yielding a product of 2.0 kb, as expected by analogy with the human BCRP sequence. cDNA clones from two independent amplifications were completely sequenced on both strands.5
Minor discrepancies between the two clones and with existing mouse ESTs were resolved by sequencing relevant portions of a Bcrp1 genomic clone derived from the 129/Ola mouse strain. A slightly shorter PCR product covering only the Bcrp1 coding sequence was used for probing blots (nucleotides 19 through 1977 in the GenBank sequence5
). A short probe for Bcrp2 covering the 3' coding region was obtained similarly by PCR based on the sequence of mouse EST AA277174.
| Results |
|---|
|
|
|---|
|
|
Cloning and Sequencing of Mouse Bcrp1.
The cross-resistance patterns and the ATP-dependent changes in mitoxantrone accumulation and efflux and their inhibition by GF120918 suggested the possibility of up-regulation of a mouse homologue of BCRP in one or more of the resistant lines. We, therefore, cloned and analyzed a mouse cDNA, Bcrp1, closely homologous to human BCRP. cDNAs containing the full Bcrp1 coding sequence were obtained by high-fidelity PCR based on existing mouse EST sequences homologous to the 5' and 3' ends of human BCRP. The cDNA sequence5
contains an extended open reading frame starting four codons downstream of an in-frame stop codon. This encodes an ABC transporter "half molecule" of 657 amino acids corresponding closely in sequence and structure to human BCRP (Fig. 2)
. The mouse Bcrp1 and human BCRP amino acid sequences are 81% identical and 86% homologous. Conservation is, as expected, very high in the ATP-binding cassette. The level of conservation between the mouse and human polypeptides is comparable with that between human MDR1 and mouse Mdr1a (87% identity) or Mdr1b (81% identity). Hydrophobicity plots of mouse Bcrp1 and human BCRP are almost identical (Fig. 2)
, increasing confidence in the assignment of six putative transmembrane domains (5
, 6)
. However, the locations of charged amino acids in the mouse sequence merited small shifts in the positions assigned to some of the transmembrane domains relative to those proposed for human BCRP. Four potential sites for N-linked glycosylation are apparent; the first two lie in what is likely to be the cytosolic part of the protein, whereas the latter two are closely spaced in the loop between the fifth and sixth putative transmembrane domains and are, thus, probably extracellular (only one is conserved in human BCRP).
|
|
| Discussion |
|---|
|
|
|---|
Mouse Bcrp1, thus, appears functionally comparable with the human BCRP as a multidrug transporter. Functional homology is also suggested by the close structural similarities between the mouse and human polypeptides. Mouse models, therefore, will likely be appropriate and valuable for investigating the biochemistry and physiological functions of the BCRP/Bcrp1 protein, and its significance for drug pharmacokinetics and drug-resistance in tumors. We are currently developing such models.
The availability of effective inhibitors of Bcrp1 will be invaluable to such studies. It is of great interest that GF120918 turns out to be an effective inhibitor of both human BCRP (20) and mouse Bcrp1. GF120918 has very low toxicity, and it has already been administered at considerable doses to both animals (19) and patients6 to inhibit P-gp activity. Pilot experiments indicate that GF120918 is nearly as efficient at inhibiting murine Bcrp1. Thus, if BCRP contributes to clinical drug resistance, GF120918 may well be attractive as a dual-action reversal/sensitizing agent, coadministered to enhance the response to chemotherapy.
The doxorubicin-selected D320 subline showed considerably greater resistance to anthracyclines bisantrene and etoposide than the other two resistant sublines (Table 1)
, whereas the Bcrp1 expression level did not differ markedly (Fig. 3)
. Evidently, additional changes occurred in this subline. Each of the above drugs affects topoisomerase II activity; therefore, it may be that topoisomerase II function is altered in the D320 line. Alternatively, the function of Bcrp1 may be changed, for instance, by a mutation that affects substrate specificity. Because Bcrp1 is an ABC transporter half molecule, it may form homodimers or heterodimers. In the latter case, although speculative, different partner molecules could confer different substrate specificities on the dimer. These possibilities are now under investigation.
Finally, we note that the ranges of drugs transported by BCRP and P-gp overlap. If BCRP does prove significant in clinical drug resistance, this significance can only increase when drug-resistance reversal agents that inhibit P-gp are used in chemotherapy. Indeed, clinical use of inhibitors for any of the drug transporters will likely bring new drug resistance mechanisms to the fore. The value of anticipating such clinical developments in the laboratory is obvious. Our results illustrate the utility of cell lines nullizygous for known MDR genes for identification and characterization of such potential new resistance mechanisms.
| ACKNOWLEDGMENTS |
|---|
| FOOTNOTES |
|---|
1 This work was supported by Dutch Cancer Society Grant NKI 97-1433. ![]()
2 To whom requests for reprints should be addressed, at Division of Experimental Therapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands. ![]()
3 The abbreviations used are: MDR, multidrug resistance; MRP, MDR-associated protein; ABC, ATP-binding cassette; BCRP, breast cancer resistance protein; P-gp, P-glycoprotein; EST, expressed sequence tag. ![]()
4 J. D. Allen, R. F. Brinkhuis, J. Wijnholds, P. Borst, and A. H. Schinkel. The contribution of multidrug transporters to basal drug resistance of mouse cell lines; manuscript in preparation. ![]()
5 The Bcrp1 sequence was deposited in GenBank under accession number AF140218. ![]()
6 J. H. M. Schellens, personal communication. ![]()
Received 6/16/99. Accepted 7/15/99.
| REFERENCES |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
T. Numbenjapon, J. Wang, D. Colcher, T. Schluep, M. E. Davis, J. Duringer, L. Kretzner, Y. Yen, S. J. Forman, and A. Raubitschek Preclinical Results of Camptothecin-Polymer Conjugate (IT-101) in Multiple Human Lymphoma Xenograft Models Clin. Cancer Res., July 1, 2009; 15(13): 4365 - 4373. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zhou, K. Schmidt, F. R. Nelson, V. Zelesky, M. D. Troutman, and B. Feng The Effect of Breast Cancer Resistance Protein and P-Glycoprotein on the Brain Penetration of Flavopiridol, Imatinib Mesylate (Gleevec), Prazosin, and 2-Methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic Acid (PF-407288) in Mice Drug Metab. Dispos., May 1, 2009; 37(5): 946 - 955. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. KATAYAMA, K. SHIBATA, J. MITSUHASHI, K. NOGUCHI, and Y. SUGIMOTO Pharmacological Interplay between Breast Cancer Resistance Protein and Gefitinib in Epidermal Growth Factor Receptor Signaling Anticancer Res, April 1, 2009; 29(4): 1059 - 1065. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Rottenberg, J. E. Jaspers, A. Kersbergen, E. van der Burg, A. O. H. Nygren, S. A. L. Zander, P. W. B. Derksen, M. de Bruin, J. Zevenhoven, A. Lau, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs PNAS, November 4, 2008; 105(44): 17079 - 17084. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. de Wolf, R. Jansen, H. Yamaguchi, M. de Haas, K. van de Wetering, J. Wijnholds, J. Beijnen, and P. Borst Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides Mol. Cancer Ther., September 1, 2008; 7(9): 3092 - 3102. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. E. Garner, E. Solon, C.-M. Lai, J. Lin, G. Luo, K. Jones, J. Duan, C. P. Decicco, T. Maduskuie, S. E. Mercer, et al. Role of P-Glycoprotein and the Intestine in the Excretion of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide] in Rodents Drug Metab. Dispos., June 1, 2008; 36(6): 1102 - 1110. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Ose, H. Kusuhara, K. Yamatsugu, M. Kanai, M. Shibasaki, T. Fujita, A. Yamamoto, and Y. Sugiyama P-glycoprotein Restricts the Penetration of Oseltamivir Across the Blood-Brain Barrier Drug Metab. Dispos., February 1, 2008; 36(2): 427 - 434. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Kobayashi, K. Saito, T. Moritomo, K. Araki, F. Takizawa, and T. Nakanishi Characterization and localization of side population (SP) cells in zebrafish kidney hematopoietic tissue Blood, February 1, 2008; 111(3): 1131 - 1137. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. A. de Vries, J. Zhao, E. Kroon, T. Buckle, J. H. Beijnen, and O. van Tellingen P-Glycoprotein and Breast Cancer Resistance Protein: Two Dominant Transporters Working Together in Limiting the Brain Penetration of Topotecan Clin. Cancer Res., November 1, 2007; 13(21): 6440 - 6449. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Ebert, A. Seidel, and A. Lampen Phytochemicals Induce Breast Cancer Resistance Protein in Caco-2 Cells and Enhance the Transport of Benzo[a]pyrene-3-sulfate Toxicol. Sci., April 1, 2007; 96(2): 227 - 236. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G. Turner, J. L. Gump, C. Zhang, J. M. Cook, D. Marchion, L. Hazlehurst, P. Munster, M. J. Schell, W. S. Dalton, and D. M. Sullivan ABCG2 expression, function, and promoter methylation in human multiple myeloma Blood, December 1, 2006; 108(12): 3881 - 3889. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Zong, S. Zhou, S. Fatima, and B. P. Sorrentino Expression of Mouse Abcg2 mRNA during Hematopoiesis Is Regulated by Alternative Use of Multiple Leader Exons and Promoters J. Biol. Chem., October 6, 2006; 281(40): 29625 - 29632. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Seamon, C. A. Rugg, S. Emanuel, A. M. Calcagno, S. V. Ambudkar, S. A. Middleton, J. Butler, V. Borowski, and L. M. Greenberger Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor. Mol. Cancer Ther., October 1, 2006; 5(10): 2459 - 2467. [Abstract] [Full Text] [PDF] |
||||
![]() |
A Mohan, M Kandalam, H L Ramkumar, L Gopal, and S Krishnakumar Stem cell markers: ABCG2 and MCM2 expression in retinoblastoma Br J Ophthalmol, July 1, 2006; 90(7): 889 - 893. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Leggas, J. C. Panetta, Y. Zhuang, J. D. Schuetz, B. Johnston, F. Bai, B. Sorrentino, S. Zhou, P. J. Houghton, and C. F. Stewart Gefitinib Modulates the Function of Multiple ATP-Binding Cassette Transporters In vivo. Cancer Res., May 1, 2006; 66(9): 4802 - 4807. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-i. Nezasa, X. Tian, M. J. Zamek-Gliszczynski, N. J. Patel, T. J. Raub, and K. L. R. Brouwer ALTERED HEPATOBILIARY DISPOSITION OF 5 (AND 6)-CARBOXY-2',7'-DICHLOROFLUORESCEIN IN Abcg2 (Bcrp1) AND Abcc2 (Mrp2) KNOCKOUT MICE Drug Metab. Dispos., April 1, 2006; 34(4): 718 - 723. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. S. Morrow, C. Peklak-Scott, B. Bishwokarma, T. E. Kute, P. K. Smitherman, and A. J. Townsend Multidrug Resistance Protein 1 (MRP1, ABCC1) Mediates Resistance to Mitoxantrone via Glutathione-Dependent Drug Efflux Mol. Pharmacol., April 1, 2006; 69(4): 1499 - 1505. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Meissner, B. Heydrich, G. Jedlitschky, H. Meyer zu Schwabedissen, I. Mosyagin, P. Dazert, L. Eckel, S. Vogelgesang, R. W. Warzok, M. Bohm, et al. The ATP-binding Cassette Transporter ABCG2 (BCRP), a Marker for Side Population Stem Cells, Is Expressed in Human Heart J. Histochem. Cytochem., February 1, 2006; 54(2): 215 - 221. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J. Dilda, A. S. Don, K. M. Tanabe, V. J. Higgins, J. D. Allen, I. W. Dawes, and P. J. Hogg Mechanism of Selectivity of an Angiogenesis Inhibitor From Screening a Genome-Wide Set of Saccharomyces cerevisiae Deletion Strains J Natl Cancer Inst, October 19, 2005; 97(20): 1539 - 1547. [Abstract] [Full Text] [PDF] |
||||
![]() |
X.-f. Zhou, X. Yang, Q. Wang, R. A. Coburn, and M. E. Morris EFFECTS OF DIHYDROPYRIDINES AND PYRIDINES ON MULTIDRUG RESISTANCE MEDIATED BY BREAST CANCER RESISTANCE PROTEIN: IN VITRO AND IN VIVO STUDIES Drug Metab. Dispos., August 1, 2005; 33(8): 1220 - 1228. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. D. Norris, J. Smith, K. Tanabe, P. Tobin, C. Flemming, G. L. Scheffer, P. Wielinga, S. L. Cohn, W. B. London, G. M. Marshall, et al. Expression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro Mol. Cancer Ther., April 1, 2005; 4(4): 547 - 553. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. H.G.P. Raaijmakers, E. P.L.M. de Grouw, L. H.H. Heuver, B. A. van der Reijden, J. H. Jansen, R. J. Scheper, G. L. Scheffer, T. J.M. de Witte, and R. A.P. Raymakers Breast Cancer Resistance Protein in Drug Resistance of Primitive CD34+38- Cells in Acute Myeloid Leukemia Clin. Cancer Res., March 15, 2005; 11(6): 2436 - 2444. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Zhou, Y. Zong, P. A. Ney, G. Nair, C. F. Stewart, and B. P. Sorrentino Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels Blood, March 15, 2005; 105(6): 2571 - 2576. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Zhang, X. Wang, K. Sagawa, and M. E. Morris FLAVONOIDS CHRYSIN AND BENZOFLAVONE, POTENT BREAST CANCER RESISTANCE PROTEIN INHIBITORS, HAVE NO SIGNIFICANT EFFECT ON TOPOTECAN PHARMACOKINETICS IN RATS OR MDR1A/1B (-/-) MICE Drug Metab. Dispos., March 1, 2005; 33(3): 341 - 348. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Ozvegy-Laczka, G. Varady, G. Koblos, O. Ujhelly, J. Cervenak, J. D. Schuetz, B. P. Sorrentino, G.-J. Koomen, A. Varadi, K. Nemet, et al. Function-dependent Conformational Changes of the ABCG2 Multidrug Transporter Modify Its Interaction with a Monoclonal Antibody on the Cell Surface J. Biol. Chem., February 11, 2005; 280(6): 4219 - 4227. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Kobayashi, I. Ieiri, T. Hirota, H. Takane, S. Maegawa, J. Kigawa, H. Suzuki, E. Nanba, M. Oshimura, N. Terakawa, et al. FUNCTIONAL ASSESSMENT OF ABCG2 (BCRP) GENE POLYMORPHISMS TO PROTEIN EXPRESSION IN HUMAN PLACENTA Drug Metab. Dispos., January 1, 2005; 33(1): 94 - 101. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-J. Lee, H. Kusuhara, J. W. Jonker, A. H. Schinkel, and Y. Sugiyama Investigation of Efflux Transport of Dehydroepiandrosterone Sulfate and Mitoxantrone at the Mouse Blood-Brain Barrier: A Minor Role of Breast Cancer Resistance Protein J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 44 - 52. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Pavek, G. Merino, E. Wagenaar, E. Bolscher, M. Novotna, J. W. Jonker, and A. H. Schinkel 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., January 1, 2005; 312(1): 144 - 152. [Abstract] [Full Text] [PDF] |
||||
![]() |
P.L. R. Ee, X. He, D. D. Ross, and W. T. Beck Modulation of breast cancer resistance protein (BCRP/ABCG2) gene expression using RNA interference Mol. Cancer Ther., December 1, 2004; 3(12): 1577 - 1584. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Tian, M. J. Zamek-Gliszczynski, P. Zhang, and K. L. R. Brouwer Modulation of Multidrug Resistance-Associated Protein 2 (Mrp2) and Mrp3 Expression and Function with Small Interfering RNA in Sandwich-Cultured Rat Hepatocytes Mol. Pharmacol., October 1, 2004; 66(4): 1004 - 1010. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Yanase, S. Tsukahara, S. Asada, E. Ishikawa, Y. Imai, and Y. Sugimoto Gefitinib reverses breast cancer resistance protein-mediated drug resistance Mol. Cancer Ther., September 1, 2004; 3(9): 1119 - 1125. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Furuchi, T. Takahashi, S. Tanaka, K. Nitta, and A. Naganuma Functions of yeast helicase Ssl2p that are essential for viability are also involved in protection from the toxicity of adriamycin Nucleic Acids Res., May 11, 2004; 32(8): 2578 - 2585. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Cisternino, C. Mercier, F. Bourasset, F. Roux, and J.-M. Scherrmann Expression, Up-Regulation, and Transport Activity of the Multidrug-Resistance Protein Abcg2 at the Mouse Blood-Brain Barrier Cancer Res., May 1, 2004; 64(9): 3296 - 3301. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nakayama, A. Kanzaki, K. Terada, M. Mutoh, K. Ogawa, T. Sugiyama, S. Takenoshita, K. Itoh, N. Yaegashi, K. Miyazaki, et al. Prognostic Value of the Cu-Transporting ATPase in Ovarian Carcinoma Patients Receiving Cisplatin-Based Chemotherapy Clin. Cancer Res., April 15, 2004; 10(8): 2804 - 2811. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Boyer, E. G. McLean, S. Aroori, P. Wilson, A. McCulla, P. D. Carey, D. B. Longley, and P. G. Johnston Characterization of p53 Wild-Type and Null Isogenic Colorectal Cancer Cell Lines Resistant to 5-Fluorouracil, Oxaliplatin, and Irinotecan Clin. Cancer Res., March 15, 2004; 10(6): 2158 - 2167. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. L. R. Ee, S. Kamalakaran, D. Tonetti, X. He, D. D. Ross, and W. T. Beck Identification of a Novel Estrogen Response Element in the Breast Cancer Resistance Protein (ABCG2) Gene Cancer Res., February 15, 2004; 64(4): 1247 - 1251. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Lassalle, H. Bastos, J. P. Louis, L. Riou, J. Testart, B. Dutrillaux, P. Fouchet, and I. Allemand `Side Population' cells in adult mouse testis express Bcrp1 gene and are enriched in spermatogonia and germinal stem cells Development, January 15, 2004; 131(2): 479 - 487. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. S. Pang MODELING OF INTESTINAL DRUG ABSORPTION: ROLES OF TRANSPORTERS AND METABOLIC ENZYMES (FOR THE GILLETTE REVIEW SERIES) Drug Metab. Dispos., December 1, 2003; 31(12): 1507 - 1519. [Full Text] [PDF] |
||||
![]() |
S. Kawabata, M. Oka, H. Soda, K. Shiozawa, K. Nakatomi, J. Tsurutani, Y. Nakamura, S. Doi, T. Kitazaki, K. Sugahara, et al. Expression and Functional Analyses of Breast Cancer Resistance Protein in Lung Cancer Clin. Cancer Res., August 1, 2003; 9(8): 3052 - 3057. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z.-S. Chen, R. W. Robey, M. G. Belinsky, I. Shchaveleva, X.-Q. Ren, Y. Sugimoto, D. D. Ross, S. E. Bates, and G. D. Kruh Transport of Methotrexate, Methotrexate Polyglutamates, and 17{beta}-Estradiol 17-({beta}-D-glucuronide) by ABCG2: Effects of Acquired Mutations at R482 on Methotrexate Transport Cancer Res., July 15, 2003; 63(14): 4048 - 4054. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Shimano, M. Satake, A. Okaya, J. Kitanaka, N. Kitanaka, M. Takemura, M. Sakagami, N. Terada, and T. Tsujimura Hepatic Oval Cells Have the Side Population Phenotype Defined by Expression of ATP-Binding Cassette Transporter ABCG2/BCRP1 Am. J. Pathol., July 1, 2003; 163(1): 3 - 9. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Rajendra, M. K. Gounder, A. Saleem, J. H. M. Schellens, D. D. Ross, S. E. Bates, P. Sinko, and E. H. Rubin Differential Effects of the Breast Cancer Resistance Protein on the Cellular Accumulation and Cytotoxicity of 9-Aminocamptothecin and 9-Nitrocamptothecin Cancer Res., June 15, 2003; 63(12): 3228 - 3233. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Janvilisri, H. Venter, S. Shahi, G. Reuter, L. Balakrishnan, and H. W. van Veen Sterol Transport by the Human Breast Cancer Resistance Protein (ABCG2) Expressed in Lactococcus lactis J. Biol. Chem., May 30, 2003; 278(23): 20645 - 20651. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Allen, S. C. van Dort, M. Buitelaar, O. van Tellingen, and A. H. Schinkel Mouse Breast Cancer Resistance Protein (Bcrp1/Abcg2) Mediates Etoposide Resistance and Transport, but Etoposide Oral Availability Is Limited Primarily by P-glycoprotein Cancer Res., March 15, 2003; 63(6): 1339 - 1344. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.M.F. Kruijtzer, J.H. Beijnen, and J.H.M. Schellens Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview Oncologist, December 1, 2002; 7(6): 516 - 530. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. Jonker, M. Buitelaar, E. Wagenaar, M. A. van der Valk, G. L. Scheffer, R. J. Scheper, T. Plosch, F. Kuipers, R. P. J. O. Elferink, H. Rosing, et al. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria PNAS, November 26, 2002; 99(24): 15649 - 15654. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. L. Volk, K. M. Farley, Y. Wu, F. Li, R. W. Robey, and E. Schneider Overexpression of Wild-Type Breast Cancer Resistance Protein Mediates Methotrexate Resistance Cancer Res., September 1, 2002; 62(17): 5035 - 5040. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M.F. Kruijtzer, J. H. Beijnen, H. Rosing, W. W. ten Bokkel Huinink, M. Schot, R. C. Jewell, E. M. Paul, and J. H.M. Schellens Increased Oral Bioavailability of Topotecan in Combination With the Breast Cancer Resistance Protein and P-Glycoprotein Inhibitor GF120918 J. Clin. Oncol., July 1, 2002; 20(13): 2943 - 2950. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Allen, S. C. Jackson, and A. H. Schinkel A Mutation Hot Spot in the Bcrp1 (Abcg2) Multidrug Transporter in Mouse Cell Lines Selected for Doxorubicin Resistance Cancer Res., April 1, 2002; 62(8): 2294 - 2299. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Allen, A. van Loevezijn, J. M. Lakhai, M. van der Valk, O. van Tellingen, G. Reid, J. H. M. Schellens, G.-J. Koomen, and A. H. Schinkel 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., April 1, 2002; 1(6): 417 - 425. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Allen and A. H. Schinkel Multidrug Resistance and Pharmacological Protection Mediated by the Breast Cancer Resistance Protein (BCRP/ABCG2) Mol. Cancer Ther., April 1, 2002; 1(6): 427 - 434. [Full Text] [PDF] |
||||
![]() |
I. F. Faneyte, P. M. P. Kristel, M. Maliepaard, G. L. Scheffer, R. J. Scheper, J. H. M. Schellens, and M. J. van de Vijver Expression of the Breast Cancer Resistance Protein in Breast Cancer Clin. Cancer Res., April 1, 2002; 8(4): 1068 - 1074. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Diah, P. K. Smitherman, J. Aldridge, E. L. Volk, E. Schneider, A. J. Townsend, and C. S. Morrow Resistance to Mitoxantrone in Multidrug-resistant MCF7 Breast Cancer Cells: Evaluation of Mitoxantrone Transport and the Role of Multidrug Resistance Protein Family Proteins Cancer Res., July 1, 2001; 61(14): 5461 - 5467. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Komatani, H. Kotani, Y. Hara, R. Nakagawa, M. Matsumoto, H. Arakawa, and S. Nishimura 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., April 1, 2001; 61(7): 2827 - 2832. [Abstract] [Full Text] |
||||
![]() |
M. Maliepaard, G. L. Scheffer, I. F. Faneyte, M. A. van Gastelen, A. C. L. M. Pijnenborg, A. H. Schinkel, M. J. van de Vijver, R. J. Scheper, and J. H. M. Schellens Subcellular Localization and Distribution of the Breast Cancer Resistance Protein Transporter in Normal Human Tissues Cancer Res., April 1, 2001; 61(8): 3458 - 3464. [Abstract] [Full Text] |
||||
![]() |
M. Maliepaard, M. A. van Gastelen, A. Tohgo, F. H. Hausheer, R. C. A. M. van Waardenburg, L. A. de Jong, D. Pluim, J. H. Beijnen, and J. H. M. Schellens 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., April 1, 2001; 7(4): 935 - 941. [Abstract] [Full Text] |
||||
![]() |
C. Erlichman, S. A. Boerner, C. G. Hallgren, R. Spieker, X.-Y. Wang, C. D. James, G. L. Scheffer, M. Maliepaard, D. D. Ross, K. C. Bible, et al. The HER Tyrosine Kinase Inhibitor CI1033 Enhances Cytotoxicity of 7-Ethyl-10-hydroxycamptothecin and Topotecan by Inhibiting Breast Cancer Resistance Protein-mediated Drug Efflux Cancer Res., January 1, 2001; 61(2): 739 - 748. [Abstract] [Full Text] |
||||
![]() |
A. Patnaik, E. Warner, M. Michael, M. J. Egorin, M. J. Moore, L. L. Siu, P. M. Fracasso, S. Rivkin, I. Kerr, M. Litchman, et al. Phase I Dose-Finding and Pharmacokinetic Study of Paclitaxel and Carboplatin With Oral Valspodar in Patients With Advanced Solid Tumors J. Clin. Oncol., November 1, 2000; 18(21): 3677 - 3689. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. A. Bardelmeijer, J. H. Beijnen, K. R. Brouwer, H. Rosing, W. J. Nooijen, J. H. M. Schellens, and O. van Tellingen Increased Oral Bioavailability of Paclitaxel by GF120918 in Mice through Selective Modulation of P-glycoprotein Clin. Cancer Res., November 1, 2000; 6(11): 4416 - 4421. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. Jonker, J. W. Smit, R. F. Brinkhuis, M. Maliepaard, J. H. Beijnen, J. H. M. Schellens, and A. H. Schinkel Role of Breast Cancer Resistance Protein in the Bioavailability and Fetal Penetration of Topotecan J Natl Cancer Inst, October 18, 2000; 92(20): 1651 - 1656. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Allen, R. F. Brinkhuis, L. v. Deemter, J. Wijnholds, and A. H. Schinkel Extensive Contribution of the Multidrug Transporters P-Glycoprotein and Mrp1 to Basal Drug Resistance Cancer Res., October 1, 2000; 60(20): 5761 - 5766. [Abstract] [Full Text] |
||||
![]() |
P. Borst, R. Evers, M. Kool, and J. Wijnholds A Family of Drug Transporters: the Multidrug Resistance-Associated Proteins J Natl Cancer Inst, August 16, 2000; 92(16): 1295 - 1302. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. L. Scheffer, M. Maliepaard, A. C. L. M. Pijnenborg, M. A. van Gastelen, M. C. de Jong, A. B. Schroeijers, D. M. van der Kolk, J. D. Allen, D. D. Ross, P. van der Valk, et al. Breast Cancer Resistance Protein Is Localized at the Plasma Membrane in Mitoxantrone- and Topotecan-resistant Cell Lines Cancer Res., May 1, 2000; 60(10): 2589 - 2593. [Abstract] [Full Text] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |