Effects of cadmium-responsive oncoprotein on cellar proto-oncogene gene expression

  Objective   To explore the molecular mechanisms potentially responsible for carcinogensis due to cadmium, the effects of cadmium-responsive oncoprotein (TEF-1δ enco ded protein) on several different genes related to cellar tumors were investigated.

  Methods   The expression of genes related to cellar tumors were detected by various monoclonal antibodies with stable transfection of mammalian cells with TEF-1δ gene and by western blot analysis.

  Results   All of the 4 different CHO cell lines stably expressed very high levels of TEF-1δ encoded protein showed over expression of cellular proto-oncogene c-fos, and the level of c-fos encoded protein(55 kDa)was very high as compared with stable-transfection of CHO cells with vector that was used as a control.All CHO cells which stably expressed very high level of TEF-1δ encoded protein demonstrated relatively high expression of cell cycle controlling gene Cyclin D1(encoded 36 kDa protein)as compared with the vector control.There were no differences between CHO cell lines stably expressed very high levels of TEF-1δ encoded protein and the vector control cells for the other oncoproteins of pan-ras, c-myc, c-jun, MDM 2, ODC, p16, p53.

  Conclusion   The translational up-regulation of cellular proto-oncogene c-fos and cell cycle controlling gene Cyclin D1 caused by over expression of the TEF-1δ, may be the molecular mechanism otentially responsible for carcinogenic potential of the novel cadmium-responsive proto-oncogen.