Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer.
Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer.
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DOI：
10.4161/cc.10.4.14864
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Glynn SA
中科院分区：
文献类型：
--
作者：
Ambs S;Glynn SA
诱导型一氧化氮合酶（NOS 2）是一种炎症应答酶（EC 1.14.13.39），其在急性和慢性炎症和组织损伤期间被诱导，作为宿主防御和伤口愈合过程的一部分。NOS 2上调导致一氧化氮（NO）产生增加，该酶可通过其启动NO依赖性信号转导，影响细胞的氧化还原状态并诱导蛋白质、脂质和DNA的修饰。NOS 2的异常表达已在许多类型的人类肿瘤中观察到。在乳腺癌中，NOS 2增加与预后不良和生存率降低的标志物相关。生长因子和细胞因子信号传导、组织重塑、NF-kB活化和缺氧是在肿瘤上皮细胞和肿瘤浸润细胞中诱导NOS 2的候选机制。NOS 2诱导将触发释放不同量的NO到肿瘤微环境中，并且可以激活致癌通路，包括Akt、表皮生长因子受体和c-Myc信号通路，并刺激肿瘤微血管形成。组成性增加的NO水平也可以选择突变型p53细胞，以克服NO激活的野生型p53的肿瘤抑制功能。最近的研究结果表明，NO诱导乳腺癌干细胞样肿瘤的特征。在这篇综述中，我们将讨论NO在肿瘤生物学和疾病进展中的作用，重点是乳腺癌，并将研究将NO增加与人类乳腺肿瘤中的基底样转录模式和不良疾病结局联系起来的机制。
Inducible nitric oxide synthase (NOS2) is an inflammation responsive enzyme (EC 1.14.13.39) that is induced during acute and chronic inflammation and tissue injury as part of the host defense and wound healing process. NOS2 up-regulation leads to increased nitric oxide (NO) production, the means by which this enzyme can initiate NO-dependent signal transduction, influence the redox state of cells and induce modifications of proteins, lipids, and DNA. Aberrant expression of NOS2 has been observed in many types of human tumors. In breast cancer, increased NOS2 is associated with markers of poor outcome and decreased survival. Growth factor and cytokine signaling, tissue remodeling, NF-kB activation, and hypoxia are candidate mechanisms that induce NOS2 in tumor epithelial and tumor-infiltrating cells. NOS2 induction will trigger the release of variable amounts of NO into the tumor microenvironment and can activate oncogenic pathways, including the Akt, epidermal growth factor receptor and c-Myc signaling pathways, and stimulate tumor microvascularization. Constitutively increased NO levels may also select for mutant p53 cells to overcome the tumor suppressor function of NO-activated wild-type p53. More recent findings suggest that NO induces stem cell-like tumor characteristics in breast cancer. In this review, we will discuss the effects of NO in tumor biology and disease progression with an emphasis on breast cancer, and will examine the mechanisms that link increased NO to a basal-like transcription pattern in human breast tumors and poor disease outcome.
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影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
5
作者：
Bentrari, F;Arnould, L;Pance, A
通讯作者：
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3.5
作者：
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通讯作者：
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DOI：
10.1093/jnci/91.1.86
发表时间：
1999-01-06
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Ambs, S;Bennett, WP;Harris, CC
通讯作者：
Harris, CC
影响因子：
11.5
作者：
Benoy, IH;Salgado, R;Dirix, LY
通讯作者：
Dirix, LY