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Activation and up‐regulation of translation initiation factor 4B contribute to arsenic‐induced transformation

Arsenic is a known human carcinogen. However, the mechanism of how arsenic induces cell transformation remains unclear. In this study, we demonstrated that long‐term exposure to sodium arsenite at low‐dose (2 µM) increases cell proliferation and neoplastic transformation in a mouse epidermal cell model, JB6 promotion‐susceptible cells. The phosphorylation of AKT and its downstream targets, 70‐kDa ribosomal protein S6 kinase (p70S6K) and translation initiation factor 4B (eIF4B), are increased in the arsenite treated cells, indicating that long‐term arsenite treatment activates AKT–p70S6K signaling pathway. In addition, long‐term exposure to arsenite up‐regulates eIF4B expression and increases the rate of translation. Knockdown of eIF4B expression resulted in inhibition of arsenic‐induced cell proliferation, transformation, and translation. Moreover, the expression of c‐Myc which is up‐regulated by long‐term arsenite treatment is inhibited by eIF4B knockdown. Taken together, these results indicate that activation and up‐regulation of eIF4B contributes to arsenic‐induced transformation in JB6 cells. Mol. Carcinog. © 2011 Wiley‐Liss, Inc.