Antisense inhibition of translation elongation factor-1 delta reverses the oncogenic potential of cadmium transformed cells.
Joseph-P; Lei-Y; Ong-T
Toxicologist 2002 Mar; 66(1-S):115
The molecular mechanisms of carcinogenesis induced by the human carcinogen-cadmium, were investigated. Differential display analysis of gene expression revealed the overexpression of translation elongation factor-1 delta sub-unit in BALB/c-3T3 cells transformed with cadmium chloride compared with the non- transformed control cells. cDNA cloning (GenBank Accession Number AF304351), expression of the encoded protein, and functional analysis of cDNA transfected NIH3T3 cells indicated that translation elongation factor-1 delta is a proto-oncogene. In order to confirm the oncogenic potential of translation elongation factor-l delta, BALB/c-3T3 cells transformed with cadmium chloride were transfected with the plasmid DNA expressing antisense TEF-I delta mRNA. Expression of the antisense translation elongation factor-l delta mRNA resulted in marked reversal of the oncogenic potential of the cadmium-transformed BALB/c- 3T3 cells. This was evidenced by a significant reduction in the number of anchor- age independent colonies developing from the transformed cells expressing antisense mRNA for translation elongation factor-1 delta compared with the vector alone-transfected control cells. Furthermore, sub-cutaneous injection of the antisense mRNA expressing transformed BALB/c-3T3 cells resulted in a significant reduction in the onset as well as the size of tumors in athymic nude mice. These results demonstrate that the cell transformation and tumorigenesis induced by the human carcinogen - cadmium, were due to the overexpression of translation elongation factor-1 delta - a novel cadmium-responsive proto-oncogene.
Genes; Cell-growth; Cell-differentiation; Protein-chemistry; Cellular-reactions; Tumorigens; Tumors; Carcinogenesis; Carcinogenicity; Cell-alteration; Cell-biology; Cell-transformation; Cellular-function; Cellular-reactions; Oncogenesis; Oncogenic-agents; Oncogenicity
Research Tools and Approaches: Cancer Research Methods
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee