Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport

Takeshi Uchiumi, Eiji Hinoshita, Sei Haga, Takanori Nakamura, Toshiya Tanaka, Satoshi Toh, Manabu Furukawa, Takeshi Kawabe, Morimasa Wada, Kazuhiro Kagotani, Katsuzumi Okumura, Kimitoshi Kohno, Shin Ichi Akiyama, Michihiko Kuwano

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

The human multidrug resistance protein (MRP) gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. We previously isolated a canalicular multispecific organic anion transporter, cMOAT1/MRP2, that belongs to the ATP binding cassette (ABC) superfamily, which is specifically expressed in liver, and cMOAT1/MRP2 is responsible for the defects in hyperbilirubinemia II/Dubin-Johnson syndrome. In this study, we isolated a new cDNA of the ABC superfamily designated cMOAT2/MRP3 that is homologous to human MRP1 and cMOAT1/MRP2: cMOAT2/MRP3 is 56% identical to MRP1 and 45% identical to cMOAT1/MRP2, respectively. Fluorescence in situ hybridization demonstrated the chromosomal locus of this gene on chromosome 17q22. The human cMOAT2 cDNA hybridized to a 6.5-kb mRNA that was mainly expressed in liver and to a lesser extent in colon, small intestine, and prostate. The cMOAT2/MRP3 gene was not overexpressed in cisplatin-resistant cell lines with increased ATP-dependent transport of cisplatin over their parental counterparts derived from human head and neck cancer and human prostatic cancer cell lines. The human cMOAT2/MRP3, a novel member of the ABC superfamily, may function as a membrane transporter in liver, colon, and prostate.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume252
Issue number1
DOIs
StatePublished - Nov 9 1998

Keywords

  • ABC transporters
  • Drug resistance
  • MRP
  • cMOAT

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Uchiumi, T., Hinoshita, E., Haga, S., Nakamura, T., Tanaka, T., Toh, S., Furukawa, M., Kawabe, T., Wada, M., Kagotani, K., Okumura, K., Kohno, K., Akiyama, S. I., & Kuwano, M. (1998). Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochemical and Biophysical Research Communications, 252(1), 103-110. https://doi.org/10.1006/bbrc.1998.9546