Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1
Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1
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DOI：
10.1016/j.bbrc.2011.09.102
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发表时间：
2011-10-28
影响因子：
3.1
通讯作者：
Jiang, Bing-Hua
中科院分区：
文献类型：
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作者：
Carpenter, Richard L.;Jiang, Yue;Jiang, Bing-Hua
砷是一种天然存在的元素，存在于有机和无机配方中。无机形式的亚砷酸盐与多种癌症类型的发展呈正相关。全世界有相当多的人口通过饮用水暴露于高砷。因此，人类暴露于砷已成为一个重大的公共卫生问题。最近的证据表明，活性氧（ROS）介导的多种变化，急性砷暴露后的细胞行为，包括激活增殖信号和血管生成。然而，ROS在慢性砷暴露介导细胞转化中的作用尚不清楚。我们发现，细胞长期暴露于亚砷酸钠增加增殖，并获得锚定非依赖性生长。这种细胞转化表型需要AKT、ERK 1/2、mTOR和p70 S6 K1的组成性激活。我们还观察到这些细胞组成性产生ROS，这是组成性激活AKT，ERK 1/2，mTOR和p70 S6 K1所必需的。通过强制过氧化氢酶表达抑制ROS水平也降低了细胞增殖和锚定非依赖性生长。这些结果表明，慢性砷暴露诱导的细胞转化是由细胞内ROS水平升高介导的，ROS介导AKT、ERK 1/2和p70 S6 K1的活化。(C)2011 Elsevier Inc. All rights reserved.
Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1. (C) 2011 Elsevier Inc. All rights reserved.