This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bordow, S. B. Articles by Norris, M. D. Search for Related Content PubMed PubMed Citation Articles by Bordow, S. B. Articles by Norris, M. D.

Expression of the Multidrug Resistance-associated Protein (MRP) Gene Correlates with Amplification and Overexpression of the N-myc Oncogene in Childhood Neuroblastoma¹

Children's Leukaemia and Cancer Research Centre, Prince of Wales Children's Hospital, High Street, Randwick, Sydney, New South Wales, 2031 [S.B. B., M. H., J. M., B. C., G. M. M., M. D. N.] and School of Paediatrics, University of New South Wales, P.O. Box 1, Kensington, Sydney, New South Wales, 2033 [M. H., G. M. M., M. D. N.], Australia

The MRP gene (Cole et al., Science (Washington DC), 258: 1650–1654, 1992) encodes a membrane-bound glycoprotein the expression of which correlates with non-P-glycoprotein-mediated multidrug resistance in a variety of cultured human cell lines. Using an RNA-polymerase chain reaction assay, expression of this gene was examined in the highly chemoresistant pediatric malignancy, neuroblastoma. MRP expression was observed in 5 human neuroblastoma cell lines and in all 25 primary neuroblastoma tumors of stage I through IVS. Tumors with amplification of the N-myc oncogene were found to have significantly higher MRP expression than those with no amplification (P = 0.0016). Expression of the MRP gene in the tumor specimens was highly correlated with expression of the N-myc gene (P = 0.0009), while expression of the MDR1 gene, encoding P-glycoprotein, was not related to expression of either the N-myc or MRP genes. Decreased expression of the N-myc oncogene in neuroblastoma cell lines SH-SY5Y and BE(2)-C, following treatment with retinoic acid, was paralleled by down-regulation of MRP gene expression, contrasting with increased expression of the MDR1 gene. Expression of the MRP gene is thus common in both primary neuroblastoma tumors and cultured cell lines, and correlates with amplification and overexpression of the N-myc oncogene, which is central to the malignant phenotype of this disease.

¹ This work was supported by the Children's Leukaemia and Cancer Foundation, Inc. (Australia), and by a grant from the Leo and Jenny Leukaemia and Cancer Foundation of Australia.

² To whom requests for reprints should be addressed.

Received 6/ 9/94. Accepted 8/18/94.

This article has been cited by other articles:

				C. Xue, M. Haber, C. Flemming, G. M. Marshall, R. B. Lock, K. L. MacKenzie, K. V. Gurova, M. D. Norris, and A. V. Gudkov p53 Determines Multidrug Sensitivity of Childhood Neuroblastoma Cancer Res., November 1, 2007; 67(21): 10351 - 10360. [Abstract] [Full Text] [PDF]

				B. B. Cheung, J. Bell, A. Raif, A. Bohlken, J. Yan, B. Roediger, A. Poljak, S. Smith, M. Lee, W. D. Thomas, et al. The Estrogen-responsive B Box Protein Is a Novel Regulator of the Retinoid Signal J. Biol. Chem., June 30, 2006; 281(26): 18246 - 18256. [Abstract] [Full Text] [PDF]

				M. Haber, J. Smith, S. B. Bordow, C. Flemming, S. L. Cohn, W. B. London, G. M. Marshall, and M. D. Norris Association of High-Level MRP1 Expression With Poor Clinical Outcome in a Large Prospective Study of Primary Neuroblastoma J. Clin. Oncol., April 1, 2006; 24(10): 1546 - 1553. [Abstract] [Full Text] [PDF]

				C. A. Burkhart, A. J. Cheng, J. Madafiglio, M. Kavallaris, M. Mili, G. M. Marshall, W. A. Weiss, L. M. Khachigian, M. D. Norris, and M. Haber Effects of MYCN Antisense Oligonucleotide Administration on Tumorigenesis in a Murine Model of Neuroblastoma J Natl Cancer Inst, September 17, 2003; 95(18): 1394 - 1403. [Abstract] [Full Text] [PDF]

				H. M. McDaid, S. Mani, H.-J. Shen, F. Muggia, D. Sonnichsen, and S. B. Horwitz Validation of the Pharmacodynamics of BMS-247550, an Analogue of Epothilone B, during a Phase I Clinical Study Clin. Cancer Res., July 1, 2002; 8(7): 2035 - 2043. [Abstract] [Full Text] [PDF]

				S. L. Cohn, W. B. London, D. Huang, H. M. Katzenstein, H. R. Salwen, T. Reinhart, J. Madafiglio, G. M. Marshall, M. D. Norris, and M. Haber MYCN Expression Is Not Prognostic of Adverse Outcome in Advanced-Stage Neuroblastoma With Nonamplified MYCN J. Clin. Oncol., November 1, 2000; 18(21): 3604 - 3613. [Abstract] [Full Text] [PDF]

				P. Chastagner, J. L. Merlin, C. Marchal, S. Hoffstetter, M. Barberi-Heyob, G. Vassal, and A. Duprez In Vivo Potentiation of Radiation Response by Topotecan in Human Rhabdomyosarcoma Xenografted into Nude Mice Clin. Cancer Res., August 1, 2000; 6(8): 3327 - 3333. [Abstract] [Full Text]

				A. K. Sarkar and J. G. Nuchtern Lysis of MYCN-amplified Neuroblastoma Cells by MYCN Peptide-specific Cytotoxic T Lymphocytes Cancer Res., April 1, 2000; 60(7): 1908 - 1913. [Abstract] [Full Text]

				J. Gilbert, M. Haber, S. B. Bordow, G. M. Marshall, and M. D. Norris Use of Tumor-Specific Gene Expression for the Differential Diagnosis of Neuroblastoma from Other Pediatric Small Round-Cell Malignancies Am. J. Pathol., July 1, 1999; 155(1): 17 - 21. [Abstract] [Full Text] [PDF]

				J. Cinatl Jr., R. Kotchetkov, M. Scholz, J. Cinatl, J.-U. Vogel, P. H. Driever, and H. W. Doerr Human Cytomegalovirus Infection Decreases Expression of Thrombospondin-1 Independent of the Tumor Suppressor Protein p53 Am. J. Pathol., July 1, 1999; 155(1): 285 - 292. [Abstract] [Full Text] [PDF]

				M. Alvarez, R. Robey, V. Sandor, K. Nishiyama, Y. Matsumoto, K. Paull, S. Bates, and T. Fojo Using the National Cancer Institute Anticancer Drug Screen to Assess the Effect of MRP Expression on Drug Sensitivity Profiles Mol. Pharmacol., November 1, 1998; 54(5): 802 - 814. [Abstract] [Full Text]

				K. Toth, M. M. Vaughan, G. Schwartz, J. S. Winston, B. S. Skenderis II, H. K. Slocum, and Y. M. Rustum Expression of the MRP and MDRI Multidrug Resistance Gene Products in 160 Untreated Human Carcinomas Studied by Immunohistochemical Methods in Formalin-Paraffin Sections International Journal of Surgical Pathology, July 1, 1998; 6(3): 145 - 154. [Abstract] [PDF]

				M.L. den Boer, R. Pieters, K.M. Kazemier, M.M.A. Rottier, C.M. Zwaan, G.J.L. Kaspers, G. Janka-Schaub, G. Henze, U. Creutzig, R.J. Scheper, et al. Relationship Between Major Vault Protein/Lung Resistance Protein, Multidrug Resistance-Associated Protein, P-Glycoprotein Expression, and Drug Resistance in Childhood Leukemia Blood, March 15, 1998; 91(6): 2092 - 2098. [Abstract] [Full Text] [PDF]

				D. Kobayashi, N. Watanabe, N. Yamauchi, N. Tsuji, T. Sato, and Y. Niitsu Endogenous Tumor Necrosis Factor as a Predictor of Doxorubicin Sensitivity in Leukemic Patients Blood, April 1, 1997; 89(7): 2472 - 2479. [Abstract] [Full Text] [PDF]

				M. D. Norris, S. B. Bordow, G. M. Marshall, P. S. Haber, S. L. Cohn, and M. Haber Expression of the Gene for Multidrug-Resistance-Associated Protein and Outcome in Patients with Neuroblastoma N. Engl. J. Med., January 25, 1996; 334(4): 231 - 238. [Abstract] [Full Text] [PDF]