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[Cancer Research 56, 4124-4129, September 15, 1996]
© 1996 American Association for Cancer Research
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A Human Canalicular Multispecific Organic Anion Transporter (cMOAT) Gene Is Overexpressed in Cisplatin-resistant Human Cancer Cell Lines with Decreased Drug Accumulation1

Ken Taniguchi, Morimasa Wada, Kimitoshi Kohno, Takanori Nakamura, Takeshi Kawabe, Mina Kawakami, Kazuhiro Kagotani, Katsuzumi Okumura, Shin-ichi Akiyama and Michihiko Kuwano2

Department of Biochemistry, Kyushu University School of Medicine, Maidashi, Fukuoka 812-82 [K. T., M. W., T. N., T. K., M. Ka., M. Ku]; Department of Molecular Biology, University of Occupational and Environmental Health, Kita-Kyushu 807 [K. Ko.]; Faculty of Bioresources, Mie University, Tsu, Mie 514 [K. Ka., K. O.]; and Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima University, Sakuraga-oka, Kagoshima 890 [S. A.], Japan

By targeting the ATP binding conserved domain in three ATP binding cassette superfamily proteins (P-glycoprotein, multidrug resistance protein, and cystic fibrosis transmembrane regulator), we isolated the cDNA of a new ATP binding cassette superfamily that was specifically enhanced in a cisplatin-resistant human head and neck cancer KB cell line. A human clone homologous to rat canalicular multispecific organic anion transporter (cMOAT) was found and designated human cMOAT. Fluorescence in situ hybridization demonstrated the chromosomal locus of the gene on chromosome 10q24. The human cMOAT cDNA hybridized a 6.5-kb mRNA that was expressed 4- to 6-fold higher by three cisplatin-resistant cell lines derived from various human tumors exhibiting decreased drug accumulation. Human cMOAT may function as a cellular cisplatin transporter.

1 Supported by a grant-in-aid for cancer research from the Ministry of Education, Science, Sports and Culture, Japan; the Fukuoka Anticancer Research Fund, Fukuoka 21st Century Medical Fund; and the Yasuda Memorial Medical Grant for Cancer Research. The nucleotide sequence reported in this paper has been deposited in the Genbank data base (Accession No. U63970).

2 To whom requests for reprints should be addressed, at Department of Biochemistry, Kyushu University School of Medicine, Maidashi, Fukuoka 812-82, Japan. Fax: 81-92-632-4198; E-mail: kuwano@biocheml.med.kyushu-u.ac.jp.

Received 6/ 4/96. Accepted 7/31/96.




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