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Up-regulation of expression of translation factors – a novel molecular mechanism for cadmium carcinogenesis

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Abstract

The molecular mechanisms potentially responsible for cadmium carcinogenesis were investigated by differential gene expression analysis of Balb/c-3T3 cells morphologically transformed with cadmium chloride. Differential display analysis of gene expression revealed overexpression of mouse Translation Initiation Factor 3 (TIF3; GenBank Accession Number AF 271072) and Translation Elongation Factor-1δ (TEF-1δ; GenBank Accession Number AF 304351) in the transformed cells compared with the control cells. The full length cDNAs for TIF3 and TEF-1δ were cloned and sequenced. Transfection of mammalian cells with an expression vector containing either TIF3 or TEF-1δ cDNA resulted in overexpression of the encoded protein. Overexpression of the cDNA-encoded TIF3 and TEF-1δ proteins in NIH3T3 cells was oncogenic as evidenced by the appearance of transformed foci capable of anchorage-independent growth on soft agar and tumorigenesis in nude mouse. Blocking the translation of TIF3 and TEF-1δ proteins using the corresponding antisense mRNA resulted in a significant reversal of the oncogenic potential of cadmium transformed Balb/c-3T3 cells as evidenced from the suppression of anchorage-independent growth on soft agar and diminished tumorigenesis in nude mouse. These findings demonstrate that the up-regulation of expression of TIF3 and TEF-1δ is a novel molecular mechanism responsible, at least in part, for cadmium carcinogenesis.

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  1. Molecular Epidemiology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA

    Pius Joseph, Yi-Xiong Lei & Tong-man Ong

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Joseph, P., Lei, YX. & Ong, Tm. Up-regulation of expression of translation factors – a novel molecular mechanism for cadmium carcinogenesis. Mol Cell Biochem 255, 93–101 (2004). https://doi.org/10.1023/B:MCBI.0000007265.38475.f7

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