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Antisense inhibition of translation initiation factor 3 reverses its oncogenic potential.

Authors
Lei-YX; Joseph-P; Ong-TM
Source
Teratog, Carcinog, Mutagen 2002 Nov; 22(6):403-409
NIOSHTIC No.
20023018
Abstract
Recently we have identified, cloned, and characterized the mouse Translation Initiation Factor 3 (TIF3, GenBank Accession Number AF 271072) as a novel cadmium-responsive proto-oncogene. Presently, additional studies regarding the oncogenic potential of TIF3 have been carried out. Transfection of NIH3T3 cells with the pcDNA3.1 expression vector containing the TIF3 cDNA in the sense (5'-->3') orientation resulted in overexpression of the encoded 36 kDa protein. Transfection-mediated overexpression of TIF3 protein resulted in transformation of the cells as evidenced from the appearance of transformed foci. Cotransfection of the cells with a mixture of plasmid DNA consisting of TIF3 cDNA in the sense and in the antisense orientation resulted in significant inhibition of translation of the TIF3 protein. Antisense (3'-->5') TIF3 mRNA-mediated inhibition of translation of TIF3 protein, furthermore, resulted in inhibition of TIF3-mediated transformation of NIH3T3 cells as evidenced from the decrease in the number of transformed foci. These results further confirm that overexpression of TIF3 is oncogenic and the antisense TIF3 mRNA expression reverses its oncogenic potential.
Keywords
Cadmium-compounds; Oncogenesis; Oncogenic-agents; Genes; Cell-transformation; Occupational-hazards; Environmental-contamination; Occupational-exposure; Workers; Exposure-levels; Kidney-damage; Liver-damage; Respiratory-system-disorders
Contact
Tong-man Ong, MS 3014, Toxicology and Molecular Biology Branch, HELD, CDC/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
TCMUD8
CAS No.
7440-43-9
Publication Date
20021101
Document Type
Journal Article
Email Address
too2@cdc.gov
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
6
ISSN
0270-3211
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Teratogenesis, Carcinogenesis, and Mutagenesis
State
WV
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