Arsenic-induced NFKB transactivation through Erks-and JNKs-dependent pathways in mouse epidermal JB6 cells

  • Chuanshu Huang
  • Jingxia Li
  • Min Ding
  • Liying Wang
  • Xianglin Shi
  • Vincent Castranova
  • Val Vallyathan
  • Ju Gong
  • Max Costa
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 34)

Abstract

Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFKB. However, the results from different groups studying the effects of arsenic on NFKB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFKB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFKB transactivation in mouse epidermal JB6 NFKB-luciferase reporter stable transfectants, C141 NFKB mass,. This induction of NFKB activity by arsenic was dose-and time-dependent. The transactivation of NFKB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFKB activity by arsenic could be dramatically inhibited by either pre-treatment of cells with PD98059 or overexpression of dominant negative JNK,. That Erks activation is required for arsenic-induced NFKB transactivation was further supported by the findings that arsenic-induced NFKB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks. (Mol Cell Biochem 222: 29-34, 2001)

Key words

arsenic NFKB MAP kinase 

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Chuanshu Huang
    • 1
  • Jingxia Li
    • 1
  • Min Ding
    • 2
  • Liying Wang
    • 2
  • Xianglin Shi
    • 2
  • Vincent Castranova
    • 2
  • Val Vallyathan
    • 2
  • Ju Gong
    • 3
  • Max Costa
    • 1
  1. 1.Nelson Institute of Environmental MedicineNew York University School of MedicineNY
  2. 2.Health Effects Laboratory DivisionNational Institute for Occupational Safety and Health, Morgantown, WVUSA
  3. 3.The Institute of NeuroscienceThe Fourth Military Medical UniversityXi’anP.R. China

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