Relationship between p53 mutations and inducible nitric oxide synthase expression in human colorectal cancer
Relationship between p53 mutations and inducible nitric oxide synthase expression in human colorectal cancer
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DOI：
10.1093/jnci/91.1.86
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发表时间：
1999-01-06
期刊：
影响因子：
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通讯作者：
Harris, CC
中科院分区：
文献类型：
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作者：
Ambs, S;Bennett, WP;Harris, CC
诱导型Ca 2+非依赖性一氧化氮合酶（NOS），也称为NOS 2，在多种人类癌症中表达（1-4），可在小鼠中产生致突变浓度的一氧化氮（NO）（5）。NOS 2是三种已知的一氧化氮合酶中活性最高的同种型（6），这三种酶还包括神经元（NOS 1）和内皮（NOS 3）同种型。只有NOS 2能够产生微摩尔范围内的持续NO浓度（7）。我们研究了由NOS 2产生的NO能够诱导p53（也称为TP 53）基因突变并有助于人类结肠癌发生的假设。我们分析了118例散发性结肠肿瘤的NOS 2表达和p53基因突变。结肠肿瘤和周围的正常组织收集自
Inducible Ca2+-independent nitric oxide synthase (NOS), also referred to as NOS2, which is expressed in a variety of human cancers (1–4), can generate mutagenic concentrations of nitric oxide (NO) in mice (5). NOS2 is the most active isoform among the three known nitric oxide synthases (6), which also include the neuronal (NOS1) and endothelial (NOS3) isoforms. Only NOS2 is capable of producing sustained NO concentrations in the micromolar range (7).We investigated the hypothesis that NO generated by NOS2 is capable of inducing mutations in the p53 (also known as TP53) gene and contributes to human colon carcinogenesis. We analyzed 118 sporadic colon tumors for NOS2 expression and p53 gene mutations. Colon tumors and surrounding normal tissues were collected from the