Antisense Inhibition of Translation Elongation Factor-1 Delta Reverses the Oncogenic Potential of Cadmium Transformed Cells

Details

• Personal Author:
  Joseph P ; Lei Y ; Ong T
• Description:
  The molecular mechanisms of carcinogenesis induced by the human carcinogen-cadmium, were investigated. Differential display analysis of gene expression revealed the overexpression of translation elongation factor-1 delta sub-unit in BALB/c-3T3 cells transformed with cadmium chloride compared with the non- transformed control cells. cDNA cloning (GenBank Accession Number AF304351), expression of the encoded protein, and functional analysis of cDNA transfected NIH3T3 cells indicated that translation elongation factor-1 delta is a proto-oncogene. In order to confirm the oncogenic potential of translation elongation factor-l delta, BALB/c-3T3 cells transformed with cadmium chloride were transfected with the plasmid DNA expressing antisense TEF-I delta mRNA. Expression of the antisense translation elongation factor-l delta mRNA resulted in marked reversal of the oncogenic potential of the cadmium-transformed BALB/c- 3T3 cells. This was evidenced by a significant reduction in the number of anchor- age independent colonies developing from the transformed cells expressing antisense mRNA for translation elongation factor-1 delta compared with the vector alone-transfected control cells. Furthermore, sub-cutaneous injection of the antisense mRNA expressing transformed BALB/c-3T3 cells resulted in a significant reduction in the onset as well as the size of tumors in athymic nude mice. These results demonstrate that the cell transformation and tumorigenesis induced by the human carcinogen - cadmium, were due to the overexpression of translation elongation factor-1 delta - a novel cadmium-responsive proto-oncogene. [Description provided by NIOSH]
• Subjects:
  Carcinogens Genetics Neoplasms Occupational Health Safety
• Keywords:
  Carcinogenesis Carcinogenicity Cell-alteration Cell-biology Cell-differentiation Cell-growth Cell-transformation Cellular-function Cellular-reactions Genes Oncogenesis Oncogenic-agents Oncogenicity Protein-chemistry Tumorigens Tumors

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• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  66
• NIOSHTIC Number:
  nn:20033729
• Citation:
  Toxicologist 2002 Mar; 66(1-S):115
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9) ; Cadmium chloride (CAS RN 10108-64-2)
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d967c0dd8ccf79d37c9bb9b2147113ec961f0762f9a03a0cb8793a8dc25dcb1c0d5dfba921aa575b75170594322fa39ccb500cb8d0df459eb9f3a23e21b0a852
• Download URL:
  https://stacks.cdc.gov/view/cdc/189190/cdc_189190_DS1.pdf
• File Type:
  [PDF - 401.74 KB ]