A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation.
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.
Taniguchi
K
K
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
Wada
M
M
Kohno
K
K
Nakamura
T
T
Kawabe
T
T
Kawakami
M
M
Kagotani
K
K
Okumura
K
K
Akiyama
S
S
Kuwano
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D002945:Cisplatin / Q000633:toxicity*; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007624:KB Cells; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms; D051381:Rats; D017386:Sequence Homology, Amino Acid; D001749:Urinary Bladder Neoplasms
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D000255:Adenosine Triphosphate; D002945:Cisplatin