Modulation of skin tumorigenesis by SOD.
Modulation of skin tumorigenesis by SOD.
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DOI：
10.1016/j.biopha.2005.03.004
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发表时间：
2005-05
期刊：
影响因子：
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通讯作者：
D. S. St. Clair;Yunfeng Zhao;L. Chaiswing;T. Oberley
中科院分区：
文献类型：
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作者：
D. S. St. Clair;Yunfeng Zhao;L. Chaiswing;T. Oberley
活性氧（ROS）的产生与癌症的发展有关。线粒体作为 ROS 生成的关键来源以及锰超氧化物歧化酶 (MnSOD) 在防止线粒体介导的细胞死亡中的作用的基础工作已经确立。 MnSOD 表达增加可抑制 ROS 的致癌作用，这一点看似矛盾，但也有充分证据表明。我们最近的研究表明，MnSOD 的过度表达可降低两阶段 7,12-二甲基苯并（a）-蒽（DMBA）/12-O-十四烷酰佛波醇-13-乙酸酯（TPA）皮肤癌发生模型中的肿瘤发生率。然而，通过杂合敲除 MnSOD 基因 (Sod 2+/–) 来减少 MnSOD 并不会导致肿瘤发病率增加。因此，线粒体 ROS 水平的调节如何改变癌症发展的结果尚不清楚。这篇综述将提供有关线粒体中 ROS 介导事件序列的背景信息，以及表明 MnSOD 的抗氧化和肿瘤抑制功能确实相互关联的证据。它还将提供有关 MnSOD 调节早期皮肤癌发生结果的机制的见解。
Generation of reactive oxygen species (ROS) has been implicated in the development of cancer. Groundwork establishing mitochondria as a critical source of ROS generation and the role of manganese superoxide dismutase (MnSOD) in preventing mitochondria-mediated cell death have been well established. In a seemingly contradictory role, it also is well documented that increased MnSOD expression suppresses the carcinogenesis effect of ROS. Our recent studies demonstrated that overexpression of MnSOD reduced tumor incidence in the two-stage 7,12-dimethylbenz(a)-anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) skin carcinogenesis model. However, reduction of MnSOD by heterozygous knockout of the MnSOD gene (Sod 2+/–) did not lead to an increase in tumor incidence. Thus, how modulation of mitochondrial ROS levels alter the outcome of developing cancer is unclear. This review will provide background information on the sequence of ROS-mediated events in the mitochondria and evidence that suggests that the antioxidant and tumor suppressor functions of MnSOD are indeed inter-related. It also will offer insights into the mechanisms by which MnSOD modulates the outcome of early stage skin carcinogenesis.