Molecular Cloning and Functional Analysis of a Novel Cadmium-Responsive Proto-Oncogene

Details

• Personal Author:
  Joseph P ; Lei Y ; Ong T ; Whong W
• Description:
  The molecular mechanisms potentially responsible for cell transformation and tumorigenesis induced by cadmium, a human carcinogen, were investigated by differential gene expression analysis of BALB/c-3T3 cells transformed with cadmium chloride (CdCl(2)). Differential display analysis of gene expression revealed consistent overexpression of mouse translation initiation factor 3 (TIF3; GenBank accession number AF271072) in the cells transformed with CdCl(2) when compared with nontransformed cells. The predicted protein encoded by TIF3 cDNA exhibited 99% similarity to human eukaryotic initiation factor 3 p36 protein. A M(r) 36,000 protein was detected in cells transfected with an expression vector containing TIF3 cDNA. Transfection of NIH3T3 cells with an expression vector containing TIF3 cDNA resulted in overexpression of the encoded protein, and this was associated with cell transformation, as evidenced by the appearance of transformed foci exhibiting anchorage-independent growth on soft agar and tumorigenic potential in nude mice. Expression of the antisense RNA against TIF3 mRNA resulted in significant reversal of oncogenic potential of the CdCl(2)-transformed BALB/c-3T3 cells. Taken together, these findings demonstrate for the first time that the cell transformation and tumorigenesis induced by CdCl(2) are due, at least in part, to the overexpression of TIF3, a novel cadmium-responsive proto-oncogene. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Air Pollution, Indoor Coal Coal Mining Disaster Planning Firefighters Fires Mining Occupational Health Safety Smoke

  More +
• Keywords:
  Cadmium-compounds Cadmium-dust Carcinogens Cell-transformation Molecular-biology Oncogenic-agents Ribonucleic-acids Tumorigenesis
• ISSN:
  0008-5472
• 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
• Volume:
  62
• Issue:
  3
• NIOSHTIC Number:
  nn:20022325
• Citation:
  Cancer Res 2002 Feb; 62(3):703-707
• Contact Point Address:
  MS 3014, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  pcj5@cdc.gov
• CAS Registry Number:
  Cadmium chloride (CAS RN 10108-64-2)
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ac99ffedbe24ce8cd4f5a14d34094019fda1f99a79dd48517c592d794f8a6f1bf824b6479324e8b83edbb473f33d18e89c878d057656c6104b562c9c678ff3d8
• Download URL:
  https://stacks.cdc.gov/view/cdc/199137/cdc_199137_DS1.pdf
• File Type:
  [PDF - 228.26 KB ]