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 Kuo, M. T. Articles by Ishikawa, T. Search for Related Content PubMed PubMed Citation Articles by Kuo, M. T. Articles by Ishikawa, T.

Frequent Coordinated Overexpression of the MRP/GS-X Pump and -Glutamylcysteine Synthetase Genes in Human Colorectal Cancers¹

Departments of Molecular Pathology [M. T. K., J-J. B.], Surgical Oncology [S. A. C.], Biomathematics [D. A. J.], and Experimental Pediatrics [T. I.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and First Department of Surgery, Tottori University, School of Medicine, 36-1 Nishimachi, Yanago 683, Japan [M. I.]

We have recently shown that multidrug resistance-associated protein (MRP) and -glutamylcysteine synthetase (-GCS) heavy subunit genes are coordinately overexpressed in cisplatin-resistant human leukemia cells (T. Ishikawa et al. J. Biol. Chem., 271: 14981–14988, 1996). Using the RNase protection assay, we examined expression levels of these genes in colon tumor and nontumorous biopsy specimens from 32 cancer patients who had not been treated with chemotherapy. Increased mRNA levels (P < 0.001) of MRP and -GCS genes were observed in 16 (50%) and 20 (62%) tumor samples, respectively. More importantly, all of the 16 (100%) MRP-overexpressing tumor specimens also exhibited higher levels of -GCS mRNA than those in the matched nontumorous specimens. The correlation coefficient between MRP and -GCS mRNA levels was r = 0.78 for all of the tumor samples studied. These results strongly suggest that MRP and -GCS genes are coordinately up-regulated during colorectal carcinogenesis.

¹ This work was supported in part by NIH Grants CA 56846 (M. T. K.) and CA 60486 (T. I.).

² To whom requests for reprints should be addressed, at The University of Texas M. D. Anderson Cancer Center, Box 89, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-3256; Fax: (713) 794-4672.

³ Present address: Medicinal Biology Department, Pfizer, Inc., Taketoyo, Aichi 470-23, Japan.

Received 5/20/96. Accepted 7/ 2/96.

This article has been cited by other articles:

				I. Qadri, M. Iwahashi, G. A. Kullak-Ublick, and F. R. Simon Hepatocyte Nuclear Factor (HNF) 1 and HNF4 Mediate Hepatic Multidrug Resistance Protein 2 Up-Regulation during Hepatitis C Virus Gene Expression Mol. Pharmacol., August 1, 2006; 70(2): 627 - 636. [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]

				I.-S. Song, S. Tatebe, W. Dai, and M. T. Kuo Delayed Mechanism for Induction of {gamma}-Glutamylcysteine Synthetase Heavy Subunit mRNA Stability by Oxidative Stress Involving p38 Mitogen-activated Protein Kinase Signaling J. Biol. Chem., August 5, 2005; 280(31): 28230 - 28240. [Abstract] [Full Text] [PDF]

				A. Shukla, T. Flanders, K. M. Lounsbury, and B. T. Mossman The {gamma}-Glutamylcysteine Synthetase and Glutathione Regulate Asbestos-induced Expression of Activator Protein-1 Family Members and Activity Cancer Res., November 1, 2004; 64(21): 7780 - 7786. [Abstract] [Full Text] [PDF]

				J. Kankesan, R. Vanama, A. Yusuf, J. J. Thiessen, V. Ling, P. M. Rao, S. Rajalakshmi, and D. S.R. Sarma Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea induced mammary carcinogenesis in rats Carcinogenesis, March 1, 2004; 25(3): 425 - 430. [Abstract] [Full Text] [PDF]

				J. Kankesan, A. Yusuf, E. Laconi, R. Vanama, G. Bradley, J. J. Thiessen, V. Ling, P. M. Rao, S. Rajalakshmi, and D. S. R. Sarma Effect of PSC 833, an inhibitor of P-glycoprotein, on 1,2-dimethylhydrazine-induced liver carcinogenesis in rats Carcinogenesis, December 1, 2003; 24(12): 1977 - 1984. [Abstract] [Full Text] [PDF]

				K. J Lenton, A. T Sane, H. Therriault, A. M Cantin, H. Payette, and J R. Wagner Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency Am. J. Clinical Nutrition, January 1, 2003; 77(1): 189 - 195. [Abstract] [Full Text] [PDF]