Alterations in the expression of translation factors as molecular markers of carcinogenesis and chemical toxicity.
Joseph P; Lei Y; O'Kernick C; Ong T
Toxicologist 2003 Mar; 72(S-1):118
Translation factors control the translation of all proteins including those vital for cell growth and differentiation as well as those involved in cellular response to chemical toxicity. Previously, we have identified, cloned, and characterized translation initiation factor 3 (TIF3) and translation elongation factor-1delta (TEF-1delta) as two novel cadmium-responsive proto-oncogenes. Cadmium-induced cell transformation and tumorigenesis were found, at least in part, to be mediated through overexpression of TIF3 and TEF-1delta. Further studies have been performed in our laboratory to determine whether alterations in the expression of various translation (initiation, elongation, and termination) factors can be used as molecular markers for carcinogenesis and chemical toxicity. By employing the real time PCR technique, we have investigated the expression levels of various translation factors in human cancer cell lines and their corresponding controls. Similarly, expression levels of the translation factors were investigated in human prostate epithelial cells, RWPE1, exposed to a cytotoxic concentration of cadmium chloride. Among the translation factors studied, the expression level of translation elongation factor 1A2 (TEF1A2) exhibited the highest alteration (approximately 2000-fold overexpression) in the cancer cell lines compared with the corresponding controls. Translation initiation factor 5A2 (TIF5A2) and translation elongation factor 1delta (TEF1 delta) also exhibited significant overexpression (10- and 5-fold overexpression, respectively) in the tumor cells compared with the corresponding control cells. Exposure of RWPE1 cells to a cytotoxic concentration of cadmium chloride also resulted in overexpression of several translation factors. These results thus demonstrate that translation factors may be cellular targets for carcinogenesis and chemical toxicity, and that alterations in their expression levels may be used as molecular marker for carcinogenesis and chemical toxicity.
Carcinogenesis; Carcinogens; Chemical-analysis; Cell-differentiation; Cell-growth; Proteins; Tumorigenesis; Cytotoxic-effects; Cytotoxicity; Tumors; Exposure-levels
Research Tools and Approaches: Cancer Research Methods
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah