AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression.

ABSTRACT

Background: AEG-1 has been proven to be tumor enhancer in gastric cancer. However, its mechanism has not yet been fully clarified. Methods: Gain-of-function and loss-of-function experiments were conducted to determine the role of eIF4E in AEG-1-induced growth of gastric cancer cells and xenografts of a nude mouse model. Western blot analysis and SRB assay were used to determine the protein expression levels and survival cell numbers. Results: Silencing the expression of AEG-1 inhibited the growth of gastric cancer cells in parallel with a decreased eIF4E and cyclin D1 expression; however, the overexpression of AEG-1 promoted cell growth and increased eIF4E and cyclin D1 expression. Moreover, the overexpression of eIF4E partially reversed the AEG-1 silencing-induced reduction of cyclin D1 and the inhibition of cell growth. An eIF4E knockdown also partially reversed the AEG-1 overexpression-induced upregulation of cyclin D1 and cell growth. Notably, manipulating the expression of eIF4E did not affect the expression of AEG-1. Finally, the silencing of AEG-1 expression inhibited the growth of SGC-7901 xenografts in parallel with the downregulation of eIF4E and cyclin D1 expression in the nude mouse model. Conclusion: AEG-1 promoted the growth of gastric cancer through upregulation of eIF4E/cyclin D1 signaling pathway.