Activation of Androgen Response Element by Cadmium: A Potential Mechanism for a Carcinogenic Effect of Cadmium in the Prostate

Details

• Personal Author:
  Barger M ; Castranova, Vincent ; Shi X ; Wang S ; Ye J
• Description:
  Cadmium is a transition metal that has been widely used in industry. Epidemiological and animal studies have demonstrated a carcinogenic effect of cadmium on the prostate. Although it has been established that androgen is required for this cancer-inducing process, it is not clear how cadmium interacts with androgen. In this study, the carcinogenic mechanism of cadmium was explored with a focus on interaction of androgen and cadmium at the gene transcription level. An androgen response luciferase reporter was used for analysis of the cadmium activity in the transient transfection assay. Human prostate epithelial cells (LNCap) and liver cells (HepG2) were transfected by the reporter. The result showed that cadmium was able to activate the reporter in the absence of androgen, and that this activation was dependent on the presence of androgen receptor. Cadmium could enhance the androgen response when both androgen and cadmium were applied together to the reporter-transfected cells. Activation of the reporter by cadmium was not associated with cell proliferation or interleukin 6 (IL-6) production, which was proposed to be involved in cadmium-induced carcinogenesis in other experimental systems. Cadmium exhibited a weak ability to induce AP-1. The results demonstrate that cadmium has an androgen-like activity in prostate epithelial cells, and this activity implies a new mechanism for the carcinogenic effect of cadmium in the prostate. [Description provided by NIOSH]
• Subjects:
  Animals Carcinogens Epidemiology Laboratories Neoplasms Occupational Health Safety
• Keywords:
  Androgen Animal Studies Author Keywords: Cadmium Cadmium Compounds Cancer Carcinogenesis Carcinogenicity HepG2 Laboratory Animals Liver Cells LNCap Prostate Cancer

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• ISSN:
  0731-8898
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  275-280
• Volume:
  19
• Issue:
  3
• NIOSHTIC Number:
  nn:20020867
• Citation:
  J Environ Pathol Toxicol Oncol 2000 Aug; 19(3):275-280
• Contact Point Address:
  Dr. Xianglin Shi, PPRB of NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  xas0@cdc.gov
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Environmental Pathology, Toxicology, and Oncology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ffb5b268d15119d5182ce39b07089e4ce0b289dd193e38b6d87dd7a5ab8da405ba7a70b906b686cb14d09656f75bc3db759fc063645b54fc1884b057868f8ad0
• Download URL:
  https://stacks.cdc.gov/view/cdc/198525/cdc_198525_DS1.pdf
• File Type:
  [PDF - 308.47 KB ]