TY - JOUR
T1 - 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
AU - Uchiumi, Takeshi
AU - Hinoshita, Eiji
AU - Haga, Sei
AU - Nakamura, Takanori
AU - Tanaka, Toshiya
AU - Toh, Satoshi
AU - Furukawa, Manabu
AU - Kawabe, Takeshi
AU - Wada, Morimasa
AU - Kagotani, Kazuhiro
AU - Okumura, Katsuzumi
AU - Kohno, Kimitoshi
AU - Akiyama, Shin Ichi
AU - Kuwano, Michihiko
N1 - Funding Information:
We thank Dr. Tito Fojo (NCI, NIH, U.S.A.) for critical reading of the manuscript. This study was supported by grants from the Min- istry of Education, Science, Sports, and Culture of Japan; the Fukuoka Anti-Cancer Research Fund; Second-Term Comprehensive, Ten-Year Strategy for Cancer Control from the Ministry of Health and Welfare; Kaibara Morikazu Medical Science Promotion Foundation; and CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (J.S.T.).
PY - 1998/11/9
Y1 - 1998/11/9
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1998.9546
DO - 10.1006/bbrc.1998.9546
M3 - Article
C2 - 9813153
AN - SCOPUS:0032501054
SN - 0006-291X
VL - 252
SP - 103
EP - 110
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
