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Science 4 December 1992:
Vol. 258. no. 5088, pp. 1650 - 1654
DOI: 10.1126/science.1360704
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Articles

Science, Vol 258, Issue 5088, 1650-1654
Copyright © 1992 by American Association for the Advancement of Science

articles

Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line

SP Cole, G Bhardwaj, JH Gerlach, JE Mackie, CE Grant, KC Almquist, AJ Stewart, EU Kurz, AM Duncan, and RG Deeley

Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.

The doxorubicin-selected lung cancer cell line H69AR is resistant to many chemotherapeutic agents. However, like most tumor samples from individuals with this disease, it does not overexpress P-glycoprotein, a transmembrane transport protein that is dependent on adenosine triphosphate (ATP) and is associated with multidrug resistance. Complementary DNA (cDNA) clones corresponding to messenger RNAs (mRNAs) overexpressed in H69AR cells were isolated. One cDNA hybridized to an mRNA of 7.8 to 8.2 kilobases that was 100- to 200-fold more expressed in H69AR cells relative to drug-sensitive parental H69 cells. Overexpression was associated with amplification of the cognate gene located on chromosome 16 at band p13.1. Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression. The mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.


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Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport.
S. H. Wright and W. H. Dantzler (2004)
Physiol Rev 84, 987-1049
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TEL/AML1 Overcomes Drug Resistance Through Transcriptional Repression of Multidrug Resistance-1 Gene Expression.
K. Asakura, H. Uchida, H. Miyachi, H. Kobayashi, Y. Miyakawa, S. D. Nimer, H. Takahashi, Y. Ikeda, and M. Kizaki (2004)
Mol. Cancer Res. 2, 339-347
   Abstract »    Full Text »    PDF »
Function of the ABC Signature Sequences in the Human Multidrug Resistance Protein 1.
X.-Q. Ren, T. Furukawa, M. Haraguchi, T. Sumizawa, S. Aoki, M. Kobayashi, and S.-i. Akiyama (2004)
Mol. Pharmacol. 65, 1536-1542
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Functions of yeast helicase Ssl2p that are essential for viability are also involved in protection from the toxicity of adriamycin.
T. Furuchi, T. Takahashi, S. Tanaka, K. Nitta, and A. Naganuma (2004)
Nucleic Acids Res. 32, 2578-2585
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Tumor Cell Responses to a Novel Glutathione S-Transferase-Activated Nitric Oxide-Releasing Prodrug.
V. J. Findlay, D. M. Townsend, J. E. Saavedra, G. S. Buzard, M. L. Citro, L. K. Keefer, X. Ji, and K. D. Tew (2004)
Mol. Pharmacol. 65, 1070-1079
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Flavonoids Are Inhibitors of Breast Cancer Resistance Protein (ABCG2)-Mediated Transport.
S. Zhang, X. Yang, and M. E. Morris (2004)
Mol. Pharmacol. 65, 1208-1216
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Identification of Proline Residues in the Core Cytoplasmic and Transmembrane Regions of Multidrug Resistance Protein 1 (MRP1/ABCC1) Important for Transport Function, Substrate Specificity, and Nucleotide Interactions.
K. Koike, G. Conseil, E. M. Leslie, R. G. Deeley, and S. P. C. Cole (2004)
J. Biol. Chem. 279, 12325-12336
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The Molecular Basis of the Action of Disulfiram as a Modulator of the Multidrug Resistance-Linked ATP Binding Cassette Transporters MDR1 (ABCB1) and MRP1 (ABCC1).
Z. E. Sauna, X.-H. Peng, K. Nandigama, S. Tekle, and S. V. Ambudkar (2004)
Mol. Pharmacol. 65, 675-684
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VX-710 (Biricodar) Increases Drug Retention and Enhances Chemosensitivity in Resistant Cells Overexpressing P-Glycoprotein, Multidrug Resistance Protein, and Breast Cancer Resistance Protein.
H. Minderman, K. L. O'Loughlin, L. Pendyala, and M. R. Baer (2004)
Clin. Cancer Res. 10, 1826-1834
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Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro.
S. K. Green, G. Francia, C. Isidoro, and R. S. Kerbel (2004)
Mol. Cancer Ther. 3, 149-159
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Chemogenomic profiling: Identifying the functional interactions of small molecules in yeast.
G. Giaever, P. Flaherty, J. Kumm, M. Proctor, C. Nislow, D. F. Jaramillo, A. M. Chu, M. I. Jordan, A. P. Arkin, and R. W. Davis (2004)
PNAS 101, 793-798
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Novel Mode of Action of Tylophorine Analogs as Antitumor Compounds.
W. Gao, W. Lam, S. Zhong, C. Kaczmarek, D. C. Baker, and Y.-C. Cheng (2004)
Cancer Res. 64, 678-688
   Abstract »    Full Text »    PDF »
The Conserved Glutamate Residue Adjacent to the Walker-B Motif Is the Catalytic Base for ATP Hydrolysis in the ATP-binding Cassette Transporter BmrA.
C. Orelle, O. Dalmas, P. Gros, A. Di Pietro, and J.-M. Jault (2003)
J. Biol. Chem. 278, 47002-47008
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Regulation of Progenitor Cell Fusion by ABCB5 P-glycoprotein, a Novel Human ATP-binding Cassette Transporter.
N. Y. Frank, S. S. Pendse, P. H. Lapchak, A. Margaryan, D. Shlain, C. Doeing, M. H. Sayegh, and M. H. Frank (2003)
J. Biol. Chem. 278, 47156-47165
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Overcoming Drug Resistance in Multiple Myeloma: The Emergence of Therapeutic Approaches to Induce Apoptosis.
H. H. Yang, M. H. Ma, R. A. Vescio, and J. R. Berenson (2003)
J. Clin. Oncol. 21, 4239-4247
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Functional Importance of Polar and Charged Amino Acid Residues in Transmembrane Helix 14 of Multidrug Resistance Protein 1 (MRP1/ABCC1): IDENTIFICATION OF AN ASPARTATE RESIDUE CRITICAL FOR CONVERSION FROM A HIGH TO LOW AFFINITY SUBSTRATE BINDING STATE.
D.-W. Zhang, H.-M. Gu, D. Situ, A. Haimeur, S. P. C. Cole, and R. G. Deeley (2003)
J. Biol. Chem. 278, 46052-46063
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Cloning and Characterization of the Murine and Rat mrp1 Promoter Regions.
M. Muredda, K.-I. Nunoya, R. A. Burtch-Wright, E. U. Kurz, S. P. C. Cole, and R. G. Deeley (2003)
Mol. Pharmacol. 64, 1259-1269
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Functional Expression of the Multidrug Resistance Protein 1 in Microglia.
S. Dallas, X. Zhu, S. Baruchel, L. Schlichter, and R. Bendayan (2003)
J. Pharmacol. Exp. Ther. 307, 282-290
   Abstract »    Full Text »    PDF »
The Role of ABC Transporters in Clinical Practice.
G. D. Leonard, T. Fojo, and S. E. Bates (2003)
Oncologist 8, 411-424
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99mTc-MIBI Imaging as a Predictor of Therapy Response in Osteosarcoma Compared with Multidrug Resistance-Associated Protein and P-Glycoprotein Expression.
Z. Burak, J.-L. Moretti, O. Ersoy, U. Sanli, M. Kantar, F. Tamgac, and G. Basdemir (2003)
J. Nucl. Med. 44, 1394-1401
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Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer.
D. E. Atkinson, S. L. Greenwood, C. P. Sibley, J. D. Glazier, and L. J. Fairbairn (2003)
Am J Physiol Cell Physiol 285, C584-C591
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ATP Binding to the First Nucleotide Binding Domain of Multidrug Resistance-associated Protein Plays a Regulatory Role at Low Nucleotide Concentration, whereas ATP Hydrolysis at the Second Plays a Dominant Role in ATP-dependent Leukotriene C4 Transport.
R. Yang, L. Cui, Y.-x. Hou, J. R. Riordan, and X.-b. Chang (2003)
J. Biol. Chem. 278, 30764-30771
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MOLECULAR CLONING AND PHARMACOLOGICAL CHARACTERIZATION OF RAT MULTIDRUG RESISTANCE PROTEIN 1 (MRP1).
K. Nunoya, C. E. Grant, D. Zhang, S. P. C. Cole, and R. G. Deeley (2003)
Drug Metab. Dispos. 31, 1016-1026
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