| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics |
Medical Sciences Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [H. Z., M. G. B., G. D. K.], and Department of Toxicology, Clemson University, Clemson, South Carolina 29670 [L. J. B.]
Multidrug resistance-associated protein (MRP)1 and canalicular multispecific organic anion transporter (cMOAT)/MRP2 are ATP-binding cassette (ABC) transporters that confer resistance to natural product cytotoxic drugs. We recently described the complete coding sequences of four human MRP/cMOAT subfamily members and found that, among these proteins, MRP3/MOAT-D is most closely related to MRP1 (58% identity; M. G. Belinsky and G. D. Kruh, Br. J. Cancer, 80: 1342–1349, 1999). In the present study, we sought to determine whether MRP3 is capable of conferring resistance to cytotoxic drugs. To address this question, human embryonic kidney 293 cells were transfected with an MRP3 expression vector, and the drug resistance phenotype of the transfected cells was analyzed. The MRP3-transfected cells displayed 
4-fold resistance to etoposide and 2-fold resistance to vincristine, compared with control transfected cells. In addition, 1.7-fold resistance was observed for the antimetabolite methotrexate. Increased resistance was not observed for several other natural product agents, including anthracyclines and Taxol. The MRP-transfected cells exhibited reduced accumulation of radiolabeled etoposide, consistent with the operation of a plasma membrane efflux pump. These results indicate that MRP3 confers resistance to some anticancer agents but that its resistance pattern is distinct from the resistance patterns of other ABC transporters involved in resistance to natural product chemotherapeutic agents.
This article has been cited by other articles:
|
|
 |
|
  C. O'Brien, G. Cavet, A. Pandita, X. Hu, L. Haydu, S. Mohan, K. Toy, C. S. Rivers, Z. Modrusan, L. C. Amler, et al. Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer Cancer Res., July 1, 2008; 68(13): 5380 - 5389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tanaka, C. Chen, J. M. Maher, and C. D. Klaassen Ischemia-Reperfusion of Rat Livers Decreases Liver and Increases Kidney Multidrug Resistance Associated Protein 2 (Mrp2) Toxicol. Sci., January 1, 2008; 101(1): 171 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Zamek-Gliszczynski, K.-i. Nezasa, X. Tian, A. S. Bridges, K. Lee, M. G. Belinsky, G. D. Kruh, and K. L. R. Brouwer Evaluation of the Role of Multidrug Resistance-Associated Protein (Mrp) 3 and Mrp4 in Hepatic Basolateral Excretion of Sulfate and Glucuronide Metabolites of Acetaminophen, 4-Methylumbelliferone, and Harmol in Abcc3-/- and Abcc4-/- Mice J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1485 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Deeley, C. Westlake, and S. P. C. Cole Transmembrane Transport of Endo- and Xenobiotics by Mammalian ATP-Binding Cassette Multidrug Resistance Proteins. Physiol Rev, July 1, 2006; 86(3): 849 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Couture, J. A. Nash, and J. Turgeon The ATP-Binding Cassette Transporters and Their Implication in Drug Disposition: A Special Look at the Heart. Pharmacol. Rev., June 1, 2006; 58(2): 244 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L.A. Plasschaert, E. S.J.M. de Bont, M. Boezen, D. M. vander Kolk, S. M.J.G. Daenen, K. N. Faber, W. A. Kamps, E. G.E. de Vries, and E. Vellenga Expression of Multidrug Resistance-Associated Proteins Predicts Prognosis in Childhood and Adult Acute Lymphoblastic Leukemia Clin. Cancer Res., December 15, 2005; 11(24): 8661 - 8668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, H. Peng, and J.-T. Zhang Expression Profiling of ABC Transporters in a Drug-Resistant Breast Cancer Cell Line Using AmpArray Mol. Pharmacol., August 1, 2005; 68(2): 430 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Belinsky, P. A. Dawson, I. Shchaveleva, L. J. Bain, R. Wang, V. Ling, Z.-S. Chen, A. Grinberg, H. Westphal, A. Klein-Szanto, et al. Analysis of the In Vivo Functions of Mrp3 Mol. Pharmacol., July 1, 2005; 68(1): 160 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Sharma, J. L. Prior, M. G. Belinsky, G. D. Kruh, and D. Piwnica-Worms Characterization of a 67Ga/68Ga Radiopharmaceutical for SPECT and PET of MDR1 P-Glycoprotein Transport Activity In Vivo: Validation in Multidrug-Resistant Tumors and at the Blood-Brain Barrier J. Nucl. Med., February 1, 2005; 46(2): 354 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hopper-Borge, Z.-S. Chen, I. Shchaveleva, M. G. Belinsky, and G. D. Kruh Analysis of the Drug Resistance Profile of Multidrug Resistance Protein 7 (ABCC10): Resistance to Docetaxel Cancer Res., July 15, 2004; 64(14): 4927 - 4930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Ifergan, A. Shafran, G. Jansen, J. H. Hooijberg, G. L. Scheffer, and Y. G. Assaraf Folate Deprivation Results in the Loss of Breast Cancer Resistance Protein (BCRP/ABCG2) Expression: A ROLE FOR BCRP IN CELLULAR FOLATE HOMEOSTASIS J. Biol. Chem., June 11, 2004; 279(24): 25527 - 25534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Schaner, D. T. Ross, G. Ciaravino, T. Sorlie, O. Troyanskaya, M. Diehn, Y. C. Wang, G. E. Duran, T. L. Sikic, S. Caldeira, et al. Gene Expression Patterns in Ovarian Carcinomas Mol. Biol. Cell, November 1, 2003; 14(11): 4376 - 4386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Leonard, T. Fojo, and S. E. Bates The Role of ABC Transporters in Clinical Practice Oncologist, October 1, 2003; 8(5): 411 - 424. [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]
|
|
|
|
 |
|
 A. C. Lockhart, R. G. Tirona, and R. B. Kim Pharmacogenetics of ATP-binding Cassette Transporters in Cancer and Chemotherapy Mol. Cancer Ther., July 1, 2003; 2(7): 685 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bodo, E. Bakos, F. Szeri, A. Varadi, and B. Sarkadi Differential Modulation of the Human Liver Conjugate Transporters MRP2 and MRP3 by Bile Acids and Organic Anions J. Biol. Chem., June 20, 2003; 278(26): 23529 - 23537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. G. Assaraf, L. Rothem, J. H. Hooijberg, M. Stark, I. Ifergan, I. Kathmann, B. A. C. Dijkmans, G. J. Peters, and G. Jansen Loss of Multidrug Resistance Protein 1 Expression and Folate Efflux Activity Results in a Highly Concentrative Folate Transport in Human Leukemia Cells J. Biol. Chem., February 21, 2003; 278(9): 6680 - 6686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hitzl, K. Klein, U. M. Zanger, P. Fritz, A. K. Nussler, P. Neuhaus, and M. F. Fromm Influence of Omeprazole on Multidrug Resistance Protein 3 Expression in Human Liver J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 524 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Oleschuk, R. G. Deeley, and S. P. C. Cole Substitution of Trp1242 of TM17 alters substrate specificity of human multidrug resistance protein 3 Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G280 - G289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Belinsky, Z.-S. Chen, I. Shchaveleva, H. Zeng, and G. D. Kruh Characterization of the Drug Resistance and Transport Properties of Multidrug Resistance Protein 6 (MRP6, ABCC6) Cancer Res., November 1, 2002; 62(21): 6172 - 6177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Haimeur, R. G. Deeley, and S. P. C. Cole Charged Amino Acids in the Sixth Transmembrane Helix of Multidrug Resistance Protein 1 (MRP1/ABCC1) Are Critical Determinants of Transport Activity J. Biol. Chem., October 25, 2002; 277(44): 41326 - 41333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. P. Lin, D. R. Johnson, R. A. Finch, M. G. Belinsky, G. D. Kruh, and A. C. Sartorelli Comparative Study of the Importance of Multidrug Resistance-associated Protein 1 and P-Glycoprotein to Drug Sensitivity in Immortalized Mouse Embryonic Fibroblasts Mol. Cancer Ther., October 1, 2002; 1(12): 1105 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. M. Fernandez, Z. Hollo, A. Kern, E. Bakos, P. A. Fischer, P. Borst, and R. Evers Role of the N-terminal Transmembrane Region of the Multidrug Resistance Protein MRP2 in Routing to the Apical Membrane in MDCKII Cells J. Biol. Chem., August 16, 2002; 277(34): 31048 - 31055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-S. Chen, K. Lee, S. Walther, R. B. Raftogianis, M. Kuwano, H. Zeng, and G. D. Kruh Analysis of Methotrexate and Folate Transport by Multidrug Resistance Protein 4 (ABCC4): MRP4 Is a Component of the Methotrexate Efflux System Cancer Res., June 1, 2002; 62(11): 3144 - 3150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-W. Zhang, S. P. C. Cole, and R. G. Deeley Determinants of the Substrate Specificity of Multidrug Resistance Protein 1. ROLE OF AMINO ACID RESIDUES WITH HYDROGEN BONDING POTENTIAL IN PREDICTED TRANSMEMBRANE HELIX 17 J. Biol. Chem., May 31, 2002; 277(23): 20934 - 20941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zelcer, T. Saeki, G. Reid, J. H. Beijnen, and P. Borst Characterization of Drug Transport by the Human Multidrug Resistance Protein 3 (ABCC3) J. Biol. Chem., November 30, 2001; 276(49): 46400 - 46407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zeng, Z.-S. Chen, M. G. Belinsky, P. A. Rea, and G. D. Kruh Transport of Methotrexate (MTX) and Folates by Multidrug Resistance Protein (MRP) 3 and MRP1: Effect of Polyglutamylation on MTX Transport Cancer Res., October 1, 2001; 61(19): 7225 - 7232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Z. Khokhar, Y. She, V. W. Rusch, and F. M. Sirotnak Experimental Therapeutics with a New 10-Deazaaminopterin in Human Mesothelioma: Further Improving Efficacy through Structural Design, Pharmacologic Modulation at the Level of MRP ATPases, and Combined Therapy with Platinums Clin. Cancer Res., October 1, 2001; 7(10): 3199 - 3205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. O. Hamilton, E. Topp, I. Makagiansar, T. Siahaan, M. Yazdanian, and K. L. Audus Multidrug Resistance-Associated Protein-1 Functional Activity in Calu-3 Cells J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1199 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yamada, K. Kawano, M. Koga, T. Matsumoto, and K. Itoh Multidrug Resistance-associated Protein 3 Is a Tumor Rejection Antigen Recognized by HLA-A2402-restricted Cytotoxic T Lymphocytes Cancer Res., September 1, 2001; 61(17): 6459 - 6466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Young, B. G. Campling, S. P. C. Cole, R. G. Deeley, and J. H. Gerlach Multidrug Resistance Proteins MRP3, MRP1, and MRP2 in Lung Cancer: Correlation of Protein Levels with Drug Response and Messenger RNA Levels Clin. Cancer Res., June 1, 2001; 7(6): 1798 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lee, A. J. P. Klein-Szanto, and G. D. Kruh Analysis of the MRP4 Drug Resistance Profile in Transfected NIH3T3 Cells J Natl Cancer Inst, December 6, 2000; 92(23): 1934 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Loging, A. Lal, I-M. Siu, T. L. Loney, C. J. Wikstrand, M. A. Marra, C. Prange, D. D. Bigner, R. L. Strausberg, and G. J. Riggins Identifying Potential Tumor Markers and Antigens by Database Mining and Rapid Expression Screening Genome Res., September 1, 2000; 10(9): 1393 - 1402. [Abstract] [Full Text]
|
|
|
|
|
|
H. Zeng, G. Liu, P. A. Rea, and G. D. Kruh Transport of Amphipathic Anions by Human Multidrug Resistance Protein 3 Cancer Res., September 1, 2000; 60(17): 4779 - 4784. [Abstract] [Full Text]
|
|
|
|
|
|
F. M. Sirotnak, H. G. Wendel, W. G. B. Bornmann, W. P. Tong, V. A. Miller, H. I. Scher, and M. G. Kris Co-administration of Probenecid, an Inhibitor of a cMOAT/MRP- like Plasma Membrane ATPase, Greatly Enhanced the Efficacy of a New 10-Deazaaminopterin against Human Solid Tumors in Vivo Clin. Cancer Res., September 1, 2000; 6(9): 3705 - 3712. [Abstract] [Full Text]
|
|
|
|
|
|
Q. Mao, R. G. Deeley, and S. P. C. Cole Functional Reconstitution of Substrate Transport by Purified Multidrug Resistance Protein MRP1 (ABCC1) in Phospholipid Vesicles J. Biol. Chem., October 27, 2000; 275(44): 34166 - 34172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-S. Chen, K. Lee, and G. D. Kruh Transport of Cyclic Nucleotides and Estradiol 17-beta -D-Glucuronide by Multidrug Resistance Protein 4. RESISTANCE TO 6-MERCAPTOPURINE AND 6-THIOGUANINE J. Biol. Chem., August 31, 2001; 276(36): 33747 - 33754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Ito, C. J. Oleschuk, C. Westlake, M. Z. Vasa, R. G. Deeley, and S. P. C. Cole Mutation of Trp1254 in the Multispecific Organic Anion Transporter, Multidrug Resistance Protein 2 (MRP2) (ABCC2), Alters Substrate Specificity and Results in Loss of Methotrexate Transport Activity J. Biol. Chem., October 5, 2001; 276(41): 38108 - 38114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ringpfeil, M. G. Lebwohl, A. M. Christiano, and J. Uitto Pseudoxanthoma elasticum: Mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter PNAS, May 23, 2000; 97(11): 6001 - 6006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wijnholds, C. A. A. M. Mol, L. van Deemter, M. de Haas, G. L. Scheffer, F. Baas, J. H. Beijnen, R. J. Scheper, S. Hatse, E. De Clercq, et al. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs PNAS, June 20, 2000; 97(13): 7476 - 7481. [Abstract] [Full Text] [PDF]
|
|
| 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 |
