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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

1998; Elsevier BV; Volume: 252; Issue: 1 Linguagem: Inglês

10.1006/bbrc.1998.9546

1090-2104

Takeshi Uchiumi, Eiji Hinoshita, S. Haga, T. Nakamura, Toshiya Tanaka, S. Toh, Manabu Furukawa, Takeshi Kawabe, Morimasa Wada, Kazuhiro Kagotani, Katsuzumi Okumura, Kimitoshi Kohno, Shin-ichi Akiyama, Michihiko Kuwano,

Pediatric Hepatobiliary Diseases and Treatments

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. Fluorescencein situhybridization 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.