Involvement of Erks activation in cadmium-induced AP-1 transactivationin vitroandin vivo

  • Chuanshu Huang
  • Qunwei Zhang
  • Jingxia Li
  • Xianglin Shi
  • Vincent Castranova
  • Gong Ju
  • Max Costa
  • Zigang Dong
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 34)

Abstract

Cadmium is a potent and effective carcinogen in rodents and has recently been accepted by IARC (International Agency for Research on Cancer) as a category 1 carcinogen. Cadmium-induced up-regulation of intracellular signaling pathways leading to increased mitogenesis is thought to be a major mechanism for the carcinogenic activity following chronic cadmium exposure. In the present study, we found that exposure of cells to cadmium induced significant activation of AP-1 and all three members of the MAP kinase family in mouse epidermal JB6 cells. The induction of AP-I activity by cadmium appears to involve activation of Erks, since the induction of AP- l activity by cadmium was blocked by pretreatment of cells with PD98058. Interestingly, the induction of AP-1 by cadmium was greatly enhanced by the chemical tumor promoter, TPA and the growth factor EGF, but not by ultraviolet C radiation.In vivostudies demonstrated that cadmium could also induce transactivation of AP-1 in AP- l -iuciferase report transgenic mice. Considering the role of AP- activation in tumor promotion, the results presented in this study provide a possible molecular mechanism for cadmium-induced carcinogenesis. (Mol Cell Biochem 222: 141-147, 2001)

Key words:

cadmium AP-1 transgenic and MAP kinase 

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Chuanshu Huang
    • 1
  • Qunwei Zhang
    • 1
  • Jingxia Li
    • 1
  • Xianglin Shi
    • 2
  • Vincent Castranova
    • 2
  • Gong Ju
    • 3
  • Max Costa
    • 1
  • Zigang Dong
    • 4
  1. 1.Nelson Institute of Environmental MedicineNew York University School of Medicine
  2. 2.Health Effects Laboratory DivisionNational Institute for Occupational Safety and HealthMorgantown
  3. 3.The Hormel InstituteUniversity of MinnesotaAustinUSA
  4. 4.The Institute of NeuroscienceThe Fourth Military Medical UniversityXi’anP.R. China

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