Up-Regulation of Expression of Translation Factors – a Novel Molecular Mechanism for Cadmium Carcinogenesis

Details

• Personal Author:
  Joseph P ; Lei Y ; Ong T
• Description:
  The molecular mechanisms potentially responsible for cadmium carcinogenesis were investigated by differential gene expression analysis of Balb/c-3T3 cells morphologically transformed with cadmium chloride. Differential display analysis of gene expression revealed overexpression of mouse Translation Initiation Factor 3 (TIF3; GenBank Accession Number AF 271072) and Translation Elongation Factor-1d (TEF-1d; GenBank Accession Number AF 304351) in the transformed cells compared with the control cells. The full length cDNAs for TIF3 and TEF-1d were cloned and sequenced. Transfection of mammalian cells with an expression vector containing either TIF3 or TEF-1d cDNA resulted in overexpression of the encoded protein. Overexpression of the cDNA-encoded TIF3 and TEF-1d proteins in NIH3T3 cells was oncogenic as evidenced by the appearance of transformed foci capable of anchorage-independent growth on soft agar and tumorigenesis in nude mouse. Blocking the translation of TIF3 and TEF-1d proteins using the corresponding antisense mRNA resulted in a significant reversal of the oncogenic potential of cadmium transformed Balb/c-3T3 cells as evidenced from the suppression of anchorage-independent growth on soft agar and diminished tumorigenesis in nude mouse. These findings demonstrate that the up-regulation of expression of TIF3 and TEF-1d is a novel molecular mechanism responsible, at least in part, for cadmium carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Air Pollution Air Pollution, Indoor Cadmium Carcinogens Irritants Metals, Heavy Occupational Health Poisoning Respiratory Tract Diseases Safety Smokers Tobacco Products

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• Keywords:
  Air-contamination Air-quality Author Keywords: Cadmium Cadmium-compounds Cadmium-poisoning Carcinogenesis Cigarette-smoking Gene-mutation Gene Expression Heavy-metals Mechanisms Respiratory-irritants Respiratory-system-disorders Translation Factors

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• ISSN:
  0300-8177
• 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:
  93-101
• Volume:
  255
• Issue:
  1
• NIOSHTIC Number:
  nn:20024217
• Citation:
  Mol Cell Biochem 2004 Jan; 255(1-2):93-101
• Contact Point Address:
  Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV
• Email:
  pcj5@cdc.gov
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9)
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• 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:fe558bb5abfd90881ab34130685f9379a9cbc1d8154f0160689de887a9ba0aaa1e219a821998244c2382850b73e0cd119802ed3b980005a6db5f6e6e55105cda
• Download URL:
  https://stacks.cdc.gov/view/cdc/196143/cdc_196143_DS1.pdf
• File Type:
  [PDF - 133.97 KB ]