Involvement of Erks Activation in Cadmium-Induced AP-1 Transactivation In Vitro and In Vivo

Details

• Personal Author:
  Castranova, Vincent ; Costa M ; Dong Z ; Huang C ; Ju G ; Li J ; Shi X ; Zhang Q
• Description:
  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 I 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-1 activity by cadmium appears to involve activation of Erks, since the induction of AP-1 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 vivo studies demonstrated that cadmium could also induce transactivation of AP-1 in AP-1-luciferase report transgenic mice. Considering the role of AP-1 activation in tumor promotion, the results presented in this study provide a possible molecular mechanism for cadmium-induced carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Cadmium Carcinogens Environmental Monitoring Growth Occupational Health Safety
• Keywords:
  AP-1 Author Keywords: Cadmium Cadmium-compounds Carcinogenesis Carcinogenicity Exposure-assessment Exposure-levels Growth-factors In-vitro-studies In-vivo-studies Transgenic And MAP Kinase

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• ISSN:
  0300-8177
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; New York ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  141-147
• Volume:
  222
• Issue:
  1
• NIOSHTIC Number:
  nn:20021757
• Citation:
  Mol Cell Biochem 2001 Jun; 222(1-2):141-147
• Contact Point Address:
  Nelson Institute of Environmental Medicine, New York University School of Medicine, NY 10016
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:10316125479db2ba6adf4e44ed0bdd4db955892b337c02e69e44c2e5b208c50ae48e10c00e6653b665e6a9ba13abc82549447de1cbdc7b4d5e7f7fe9d569d78b
• Download URL:
  https://stacks.cdc.gov/view/cdc/198866/cdc_198866_DS1.pdf
• File Type:
  [PDF - 90.64 KB ]