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 cas sette superfamily proteins (P-glycoprotein, multidrug resistance prote in, and cystic fibrosis transmembrane regulator), we isolated the cDNA of a new ATP binding cassette superfamily that was specifically enhan ced in a cisplatin-resistant human head and neck cancer KB cell line. A human clone homologous to rat canalicular multispecific organic anio n transporter (cMOAT) was found and designated human cMOAT. Fluorescen ce in situ hybridization demonstrated the chromosomal locus of the gen e on chromosome 10q24. The human cMOAT cDNA hybridized a 6.5-kb mRNA t hat was expressed 4- to 6-fold higher by three cisplatin-resistant cel l lines derived from various human tumors exhibiting decreased drug ac cumulation. Human cMOAT may function as a cellular cisplatin transport er.