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.
Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, USA.
Yong
Y
Zhang
Qing
Q
Wang
Xiaoling
X
Guo
Robert
R
Miller
Yinglu
Y
Guo
Hsin-Sheng
HS
Yang
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D016259:Genes, myc; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015854:Up-Regulation
D039642:Eukaryotic Initiation Factors; C031799:eIF-4B; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D001151:Arsenic
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