HIGH-LEVELS OF EXPRESSION OF THE NAD(P)H-QUINONE OXIDOREDUCTASE (NQO1) GENE IN TUMOR-CELLS COMPARED TO NORMAL-CELLS OF THE SAME ORIGIN
HIGH-LEVELS OF EXPRESSION OF THE NAD(P)H-QUINONE OXIDOREDUCTASE (NQO1) GENE IN TUMOR-CELLS COMPARED TO NORMAL-CELLS OF THE SAME ORIGIN
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DOI：
10.1016/0006-2952(91)90284-c
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发表时间：
1991-08-08
影响因子：
5.8
通讯作者：
JAISWAL, AK
中科院分区：
文献类型：
--
作者：
CRESTEIL, T;JAISWAL, AK
NAD(P)H：醌氧化还原酶（NQO1）是一种黄蛋白，它催化醌和偶氮染料的双电子还原，从而阻止细胞色素P450还原酶催化的单电子还原可能产生的自由基和有毒氧代谢物的形成。RNA分析表明，肝癌患者肝脏肿瘤和肿瘤周围组织中NQO1基因的表达水平比正常人高20- 50倍。在人肝母细胞瘤（Hep-G2）细胞中，NQO1 mRNA的表达水平也比正常肝脏高约50倍。通过对人类NQO1基因启动子进行缺失诱变并随后转染到肝和非肝细胞系中，已经鉴定出一个1.42 kb的DNA片段包含负责NQO1基因在肿瘤细胞中高水平表达的顺式作用元件。
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.