Translation elongation factor 1 delta sub-unit is a novel cadmium-responsive proto-oncogene.
Joseph P; Lei Y; Ong T
Mutat Res 2001 Oct; 483(Suppl 1):S77
A large number of workers are potentially exposed to cadmium (Cd) in a variety of occupational settings. Cd has been classified by the International Agency for Research on Cancer (IARC) as a human carcinogen. However, little is known regarding the potential mechanisms of Cd carcinogenesis. Using BALB/c-3T3 cell transformation and nude mouse tumorigenesis models, we have investigated the molecular mechanism(s) responsible for cell transformation and tumorigenesis induced by Cd. Differential display analysis of gene expression revealed consistent and reproducible overexpression of a novel gene, translation elongation factor 1 delta sub-unit (TEF) in the transformed cells compared with the control, non-transformed cells. Similar overexpression of TEF was noticed in the cell lines developed from tumors grown in nude mice subcutaneously injected with the transformed cells. Nucleotide sequence analysis of the full-length cDNA (GenBank Accession Number AF304351) cloned from the transformed cells revealed and open reading frame encoding a predicted protein of 281 amino acids. A 31 KDa protein was detected in chinese hamster ovary cells and in monkey kidney COS7 cells transfected with an expression vector containing the entire coding region of TEF cDNA. Transfection of NIH3T3 cells with an expression vector containing the TEF cDNA resulted in its overexpression and this was assocated with cell transformation as evidenced by the appearance of the transformed foci. Taken together, these findings demonstrate that the cell transformation and tumorigenesis induced by Cd are due, at least in part, to the overexpression of TEF - a novel cellular protooncogene.
Cadmium-compounds; Exposure-levels; Work-environment; Carcinogens; Carcinogenesis; Cell-transformation; Tumors; Workers; Occupational-exposure; Laboratory-animals; Animals; Animal-studies; Tumorigens; Tumorigenesis; Models
Toxicology and Molecular Biology Branch, CDC/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505