High levels of expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin.
NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein which catalyzes the two-electron reduction of quinones and azo-dyes and thus prevents the formation of free radicals and toxic oxygen metabolites that may be generated by the one-electron reductions catalyzed by cytochrome P450 reductase. Analysis of RNA indicated 20- to 50-fold higher levels of NQO1 gene expression in the liver tumors and in the tissue surrounding the tumors of patients with hepatocarcinoma than in normal individuals. An approximately 50-fold higher level of NQO1 mRNA was also observed in human hepatoblastoma (Hep-G2) cells than in normal liver. By deletion mutagenesis in the human NQO1 gene promoter and subsequent transfection into hepatic and nonhepatic cell lines, a 1.42 kb DNA segment has been identified to contain cis-acting elements responsible for high levels of expression of the NQO1 gene in tumor cells.
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Laboratoire de Biochimie, INSERM U75, CHU Necker, Paris, France.
Jaiswal
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D001482:Base Composition; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D015500:Chloramphenicol O-Acetyltransferase; D005091:Exons; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D016296:Mutagenesis; D016660:NAD(P)H Dehydrogenase (Quinone); D010957:Plasmids; D011401:Promoter Regions, Genetic; D011808:Quinone Reductases / Q000235:genetics*; D012333:RNA, Messenger / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000302:isolation & purification; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D015500:Chloramphenicol O-Acetyltransferase