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Mol Carcinog. 2011 Jul;50(7):528-38. doi: 10.1002/mc.20733. Epub 2011 Jan 25.

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

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1
Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, USA.

Abstract

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.

PMID:
21268130
PMCID:
PMC3110507
DOI:
10.1002/mc.20733
[Indexed for MEDLINE]
Free PMC Article
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