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Arsenic‐induced NFκβ transactivation through Erks‐ and JNKs‐dependent pathways in mouse epidermal JB6 cells

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Abstract

Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP‐1 and NFκB. However, the results from different groups studying the effects of arsenic on NFκB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFκB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFκB transactivation in mouse epidermal JB6 NFκB‐luciferase reporter stable transfectants, C141 NFκB mass1. This induction of NFκB activity by arsenic was dose‐ and time‐dependent. The transactivation of NFκB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFκB activity by arsenic could be dramatically inhibited by either pre‐treatment of cells with PD98059 or overexpression of dominant negative JNK1. That Erks activation is required for arsenic‐induced NFκB transactivation was further supported by the findings that arsenic‐induced NFκB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.

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Authors and Affiliations

  1. Nelson Institute of Environmental Medicine, New York University School of Medicine, NY, 10016, USA

    Chuanshu Huang, Jingxia Li & Max Costa

  2. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

    Min Ding, Liying Wang, Xianglin Shi, Vincent Castranova & Val Vallyathan

  3. The Institute of Neuroscience, The Fourth Military Medical University, Xi'an, 710032, P.R. China

    Gong Ju

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  1. Chuanshu Huang
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  2. Jingxia Li
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  3. Min Ding
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  4. Liying Wang
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  6. Vincent Castranova
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  9. Max Costa
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Correspondence to Chuanshu Huang.

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Huang, C., Li, J., Ding, M. et al. Arsenic‐induced NFκβ transactivation through Erks‐ and JNKs‐dependent pathways in mouse epidermal JB6 cells. Mol Cell Biochem 222, 29–34 (2001). https://doi.org/10.1023/A:1017974131948

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  • DOI: https://doi.org/10.1023/A:1017974131948

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