Blocking the translation elongation factor‐1δ 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-1δ sub-unit (TEF-1δ, GenBank Accession Number AF304351) as a novel cadmium-responsive proto-oncogene. Presently, additional studies regarding the oncogenic potential of TEF-1δ have been carried out. Transfection of NIH3T3 cells with the pcDNA3.1 expression vector containing the TEF-1δ cDNA in the sense (5′3′) orientation resulted in overexpression of the encoded 31 kDa protein. Transfection-mediated overexpression of TEF-1δ 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-1δ cDNA in the sense (5′3′) and in the antisense (3′5′) orientation resulted in significant inhibition of translation of the TEF-1δ protein. Antisense TEF-1δ mRNA-mediated inhibition of translation of TEF-1δ protein, furthermore, resulted in inhibition of TEF-1δ-mediated transformation of NIH3T3 cells as evidenced from the decrease in the number of transformed foci. These results further confirm that overexpression of TEF-1δ is oncogenic and the antisense TEF-1δ mRNA expression reverses its oncogenic potential. Teratogenesis Carcinog. Mutagen. 22:377–383, 2002. © 2002 Wiley-Liss, Inc.