[Up-regulation of human chorionic gonadotropin alpha subunit gene and human mitochondrial cytochrome c oxidase subunit II gene in cis-Diamminedichloroplatinum(II)-resistant human head and neck squamous carcinoma cells].
The resistance of head and neck squamous carcinoma cells (HNSCCs) to cis-Diamminedichloroplatinum(II) (CDDP), which is widely used for the treatment of many malignancies, is a serious problem in the clinic. The mechanism by which cancer cells get resistant to this compound has not been completely understood. To elucidate the mechanism, we compared gene expression in the cells sensitive to CDDP with that in the resistant variants using fluorescent differential display technique. Side-by-side comparison on a sequence gel demonstrated that 105 genes were differentially expressed between KB, a human oral SCC line, and KB/cDDP, which was developed from KB and shows 2.5-fold increases in resistance to CDDP, as well as between HEp2, a human laryngeal SCC line, and its cDDP-resistant variants. Several candidates for the CDDP resistance related genes have been cloned by the following re-amplifications. Northern blot analysis revealed that human chorionic gonadotropin alpha subunit gene and human mitochondrial cytochrome c oxidase subunit II gene were expressed higher in KB/cDDP than in KB parental cells. Our results suggest that these two genes are associated with CDDP resistance and that human chorionic gonadotropin alpha subunit gene product is potentially a clinical biomarker for the resistance to CDDP.
Higuchi
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Department of Otolaryngology, Hokkaido University School of Medicine, Sapporo, Japan.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D006063:Chorionic Gonadotropin / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006063:Chorionic Gonadotropin; D005819:Genetic Markers; D003576:Electron Transport Complex IV; D002945:Cisplatin