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Genomic structure, gene expression, and promoter analysis of human multidrug resistance-associated protein 7

Journal of Biomedical Science volume 10, pages 98–110 (2003)Cite this article

Abstract

The multidrug resistance-associated protein (MRP) subfamily transporters associated with anticancer drug efflux are attributed to the multidrug-resistance of cancer cells. The genomic organization of human multidrug resistance-associated protein 7 (MRP7) was identified. The humanMRP7 gene, consisting of 22 exons and 21 introns, greatly differs from other members of the human MRP subfamily. A splicing variant of humanMRP7, MRP7A, expressed in most human tissues, was also characterized. The 1.93-kb promoter region ofMRP7 was isolated and shown to support luciferase activity at a level 4- to 5-fold greater than that of the SV40 promoter. BasalMRP7 gene expression was regulated by 2 regions in the 5′-flanking region at −1,780–1,287 bp, and at −611 to −208 bp. In Madin-Darby canine kidney (MDCK) cells, MRP7 promoter activity was increased by 226% by genotoxic 2-acetylaminofluorene and 347% by the histone deacetylase inhibitor, trichostatin A. The protein was expressed in the membrane fraction of transfected MDCK cells.

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Affiliations

  1. Department of Food Nutrition, Chung-Hwa College of Medical Technology, Taiwan, ROC

    Hsin-hsin Kao

  2. Graduate Institute of Pharmacology, National Cheng Kung University, Taiwan, ROC

    Hsin-hsin Kao & Jin-ding Huang

  3. Lawrence Berkeley National Laboratory, Berkeley, Calif., USA

    Jan-fang Cheng

  4. Graduate Institute of Biochemistry Medical College, National Cheng Kung University, 701, Tainan, Taiwan (ROC)

    Ming-shi Chang

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  1. Hsin-hsin Kao
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  2. Ming-shi Chang
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  4. Jin-ding Huang
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Kao, Hh., Chang, Ms., Cheng, Jf. et al. Genomic structure, gene expression, and promoter analysis of human multidrug resistance-associated protein 7. J Biomed Sci 10, 98–110 (2003). https://doi.org/10.1007/BF02256002

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  • DOI: https://doi.org/10.1007/BF02256002

Key Words

  • Multidrug resistance
  • ABC transporter
  • MRP7
  • Genomic organization
  • Promoter analysis