Activation and up-regulation of translation initiation factor 4B contribute to arsenic-induced transformation.
Activation and up-regulation of translation initiation factor 4B contribute to arsenic-induced transformation.
复制标题
翻译起始因子 4B 的激活和上调有助于砷诱导的转化。
DOI：
10.1002/mc.20733
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发表时间：
2011
影响因子：
4.6
通讯作者：
Yang,Hsin-Sheng
中科院分区：
文献类型：
--
作者：
Zhang,Yong;Wang,Qing;Guo,Xiaoling;Miller,Robert;Guo,Yinglu;Yang,Hsin-Sheng
砷是一种已知的人类致癌物质。然而，砷如何诱导细胞转化的机制仍不清楚。在这项研究中，我们证明了长期暴露于低剂量（2 μM）的亚砷酸钠会增加小鼠表皮细胞模型（JB 6促进易感细胞）中的细胞增殖和肿瘤转化。在亚砷酸盐处理的细胞中，AKT及其下游靶点70 kDa核糖体蛋白S6激酶（p70 S6 K）和翻译起始因子4 B（eIF 4 B）的磷酸化增加，表明长期亚砷酸盐处理激活AKT-p70 S6 K信号通路。此外，长期暴露于亚砷酸盐会上调eIF 4 B的表达，并增加翻译速率。eIF 4 B表达的敲低导致砷诱导的细胞增殖、转化和翻译的抑制。此外，通过长期亚砷酸盐处理上调的c-Myc的表达被eIF 4 B敲低抑制。总之，这些结果表明eIF 4 B的激活和上调有助于砷诱导的JB 6细胞转化。摩尔巨蟹座© 2011 Wiley‐利斯公司
Arsenic is a known human carcinogen. However, the mechanism of how arsenic induces cell transformation remains unclear. In this study, we demonstrated that long‐term exposure to sodium arsenite at low‐dose (2 µM) increases cell proliferation and neoplastic transformation in a mouse epidermal cell model, JB6 promotion‐susceptible cells. The phosphorylation of AKT and its downstream targets, 70‐kDa ribosomal protein S6 kinase (p70S6K) and translation initiation factor 4B (eIF4B), are increased in the arsenite treated cells, indicating that long‐term arsenite treatment activates AKT–p70S6K signaling pathway. In addition, long‐term exposure to arsenite up‐regulates eIF4B expression and increases the rate of translation. Knockdown of eIF4B expression resulted in inhibition of arsenic‐induced cell proliferation, transformation, and translation. Moreover, the expression of c‐Myc which is up‐regulated by long‐term arsenite treatment is inhibited by eIF4B knockdown. Taken together, these results indicate that activation and up‐regulation of eIF4B contributes to arsenic‐induced transformation in JB6 cells. Mol. Carcinog. © 2011 Wiley‐Liss, Inc.