The NAD(P)H:Quinone Oxidoreductase 1 induces cell cycle progression and proliferation of melanoma cells
The NAD(P)H:Quinone Oxidoreductase 1 induces cell cycle progression and proliferation of melanoma cells
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DOI：
10.1016/j.freeradbiomed.2010.03.003
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发表时间：
2010-06-15
影响因子：
7.4
通讯作者：
Li, Gang
中科院分区：
文献类型：
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作者：
Garate, Marco;Wani, Aijaz A.;Li, Gang
氧化还原酶NQO 1在维持细胞内稳态中起着重要作用。NQO 1主要是一种细胞溶质酶，催化醌类的代谢，存在于几乎所有组织类型中，提供对不同应激的保护，包括外源性物质、氧化剂、紫外线和电离辐射。这种酶在许多癌组织中过表达，其在癌发生中的功能尚不清楚。由于NQO 1在黑色素瘤发病机制中作用的信息相对缺乏，我们试图确定NQO 1在黑色素瘤细胞增殖中的表达和基本功能。我们发现，NQO 1在大多数黑色素瘤细胞系中相对于黑素细胞过表达。此外，该氧化还原酶的表达通过上调细胞周期蛋白A2、B1和D1的表达显著诱导细胞周期进展，导致黑素瘤细胞增殖。我们的研究结果还表明，NQO 1是NE-κ B p50的上游调节因子，NE-κ B p50是与黑色素瘤进展和患者预后不良相关的因子。有趣的是，我们发现NQO 1稳定了反式激活因子BCL 3，而BCL 3又上调了NF-κ B p50。更重要的是，我们的研究结果还表明，NE-κ B p50与NQO 1的表达相关，并介导其在黑色素瘤细胞增殖中的作用。(C)2010年爱思唯尔公司All rights reserved.
The oxidoreductase NQO1 plays a prominent role in maintaining the cellular homeostasis. NQO1 is mainly a cytosolic enzyme which catalyzes the metabolism of quinones and is present in almost all tissue types providing protection against different stresses including xenobiotics, oxidants, UV light, and ionizing radiation. This enzyme is overexpressed in many cancerous tissues and its function in carcinogenesis remains unclear. Due to the relative lack of information on the role of NQO1 in melanoma pathogenesis, we attempted to determine the expression and basic function of NQO1 in melanoma cell proliferation. We found that NQO1 is overexpressed in most melanoma cell lines with respect to melanocytes. Furthermore, the expression of this oxidoreductase significantly induces cell cycle progression by upregulating the expression of cyclins A2, B1 and D1, leading to the proliferation of melanoma cells. Our results also indicate that NQO1 is an upstream regulator of NE-kappa B p50, a factor linked to melanoma progression and poor patient prognosis. Interestingly, we found that NQO1 stabilizes the transactivator BCL3, which in turn upregulates NF-kappa B p50. More importantly, our results also indicate that NE-kappa B p50 correlates with the expression of NQO1 and mediates its role in the proliferation of melanoma cells. (C) 2010 Elsevier Inc. All rights reserved.