Molecular Changes During Arsenic-Induced Cell Transformation
Molecular Changes During Arsenic-Induced Cell Transformation
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DOI：
10.1002/jcp.22683
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发表时间：
2011-12-01
影响因子：
5.6
通讯作者：
Chiu, Jen-Fu
中科院分区：
文献类型：
--
作者：
Li, Guanwu;Lee, Lai-Sheung;Chiu, Jen-Fu
砷及其衍生物是自然界中广泛存在的类金属化合物。众所周知，砷会导致皮肤癌、肝癌、肺癌、肾癌和膀胱癌。虽然已经提出了许多致癌途径，但确切的分子机制仍有待阐明。为了进一步表征氧化应激在砷通过活性氧（ROS）介导的Ras/Erk途径诱导的细胞转化中的作用，我们在此证明了砷诱导的大鼠肺上皮细胞（LEC）转化、上皮-间质转化、细胞外信号调节激酶信号通路的刺激以及细胞增殖的增强。然而，没有证据表明磷酸肌醇3-激酶/蛋白激酶B途径在亚砷酸盐诱导的转化LEC激活。由于活性氧参与亚砷酸钠诱导的LEC细胞转化，氧化还原状态调节蛋白（铜/锌SOD和硫氧还蛋白）和亚砷酸钠诱导的LEC细胞转化显着抑制同时处理的抗氧化剂。我们的实验结果清楚地表明，诱导p-ERK和细胞增殖的亚砷酸盐介导的氧化应激，因为抗氧化剂可以抑制亚砷酸盐诱导的细胞转化。J.细胞。226：3225-3232，2011。(C)2011 Wiley Periodicals，Inc.
Arsenic and its derivatives are naturally occurring metalloid compounds widely distributed in the environment. Arsenics are known to cause cancers of the skin, liver, lung, kidney, and bladder. Although numerous carcinogenic pathways have been proposed, the exact molecular mechanisms remain to be delineated. To further characterize the role of oxidative stress in arsenite-induced cell transformation via the reactive oxygen species (ROS)-mediated Ras/Erk pathway, here we demonstrated arsenite-induced rat lung epithelial cell (LEC) transformation, epithelial-mesenchymal transition, stimulation of the extracellular signal-regulated kinase signaling pathway, and enhancement of cell proliferation. However, there was no evidence of activation of the phosphoinositide 3-kinase/protein kinase B pathway in arsenite-induced transformed LECs. Since ROS is involved in arsenite-induced LEC cell transformation, Redox-status regulatory proteins (Cu/Zn SOD and thioredoxin) and arsenite-induced LEC cell transformation were significantly inhibited by concurrent treatment with the antioxidants. Our experimental results clearly demonstrated that induction of p-ERK and cell proliferation by arsenite is mediated via oxidative stress, since antioxidants can inhibit arsenite-induced cell transformation. J. Cell. Physiol. 226: 3225-3232, 2011. (C) 2011 Wiley Periodicals, Inc.