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Antisense inhibition of translation initiation factor 3 reverses its oncogenic potential

Yi-Xiong Lei1, Pius Joseph, Tong-Man Ong

  • 1Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia.

Teratogenesis, Carcinogenesis, and Mutagenesis
|October 24, 2002
PubMed

Insights

Mouse Translation Initiation Factor 3 (TIF3) overexpression transforms cells, acting as a proto-oncogene. Antisense TIF3 mRNA inhibits this transformation, reversing its oncogenic potential and confirming TIF3

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • The mouse Translation Initiation Factor 3 (TIF3) was identified as a novel cadmium-responsive proto-oncogene.
  • Further investigation into the oncogenic potential of TIF3 is warranted.

Purpose of the Study:

  • To investigate the oncogenic potential of TIF3.
  • To determine if antisense TIF3 mRNA can reverse TIF3-mediated transformation.

Main Methods:

  • NIH3T3 cells were transfected with TIF3 cDNA in sense orientation for overexpression.
  • Cells were cotransfected with sense and antisense TIF3 cDNA to inhibit translation.
  • Transformation was assessed by the appearance and number of transformed foci.

Main Results:

  • Overexpression of TIF3 protein in NIH3T3 cells led to cell transformation, indicated by transformed foci.
  • Cotransfection with antisense TIF3 mRNA significantly inhibited TIF3 protein translation.
  • Inhibition of TIF3 protein translation by antisense mRNA reversed the TIF3-mediated transformation, reducing transformed foci.

Conclusions:

  • Overexpression of TIF3 is confirmed to be oncogenic.
  • Antisense TIF3 mRNA effectively reverses the oncogenic potential of TIF3.
  • These findings highlight TIF3 as a potential therapeutic target in cancer.

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