Blocking the translation elongation factor-1 delta with its antisense mRNA results in a significant reversal of its oncogenic potential.
In spite of the strong evidence for the carcinogenic activity of cadmium and its related compounds, the underlying molecular mechanisms that lead to malignant transformation in cells exposed to cadmium remain unknown. Recently, Joseph et al. [J. Biol. Chem. 227:6131-6136, 2002] have identified, cloned, and characterized the mouse Translation Elongation Factor-1 delta sub-unit (TEF-1 delta, GenBank Accession Number AF304351) as a novel cadmium-responsive proto-oncogene. Presently, additional studies regarding the oncogenic potential of TEF-1 delta have been carried out. Transfection of NIH3T3 cells with the pcDNA3.1 expression vector containing the TEF-1 delta cDNA in the sense (5'-->3') orientation resulted in overexpression of the encoded 31 kDa protein. Transfection-mediated overexpression of TEF-1 delta 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 TEF-1 delta cDNA in the sense (5'-->3') and in the antisense (3'-->5') orientation resulted in significant inhibition of translation of the TEF-1 delta protein. Antisense TEF-1 delta mRNA-mediated inhibition of translation of TEF-1 delta protein, furthermore, resulted in inhibition of TEF-1 delta-mediated transformation of NIH3T3 cells as evidenced from the decrease in the number of transformed foci. These results further confirm that overexpression of TEF-1 delta is oncogenic and the antisense TEF-1 delta mRNA expression reverses its oncogenic potential.
Lei
Yi-Xiong
YX
Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou, People's Republic of China. ybl3@cdc.gov
Chen
Jia-Kun
JK
Wu
Zhong-Liang
ZL
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger