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.
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.
Uchiumi
T
T
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Maidashi, 812-8582, USA. uchiumi@biochem1.med.kyushu-u.ac.jp
Hinoshita
E
E
Haga
S
S
Nakamura
T
T
Tanaka
T
T
Toh
S
S
Furukawa
M
M
Kawabe
T
T
Wada
M
M
Kagotani
K
K
Okumura
K
K
Kohno
K
K
Akiyama
S
S
Kuwano
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D027321:Anion Transport Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007624:KB Cells; D008297:Male; D008969:Molecular Sequence Data; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D009928:Organ Specificity; D011247:Pregnancy; D011471:Prostatic Neoplasms; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000255:Adenosine Triphosphate; D027321:Anion Transport Proteins; D002352:Carrier Proteins; D002945:Cisplatin; D004268:DNA-Binding Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; C000715087:ABCC2 protein, human; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1