Abstract
Recent studies suggested that hypoxia modulate epithelial-mesenchymal transition (EMT) process. It was also demonstrated that the biological activities of PTEN, by which cell proliferation and migration are involved, could be regulated by phosphorylation sites in its c-terminal tail. In this study, we analyzed whether gene modulation of PTEN phosphorylation sites could inhibit hypoxia-induced phenotype alterations through EMT in lung cancer cells. GFP and GFP-PTENmut were transduced into lung cancer H358 with the doxycycline (Dox) inducible gene expression system. Dox-induced expression of GFP and GFP-PTENmut in H358 were confirmed by western blot analysis. Both the Dox-untreated cells with GFP or GFP-PTEN under hypoxic condition showed the decreasing expression of E-cadherin and the de novo expression of fibronectin through EMT and significantly increased the migration ability. Only the Dox-treated cells with GFP-PTENmut kept the expression E-cadherin and inhibited the de novo expression of fibronectin against hypoxia condition. Furthermore, these cells showed the significant repression of cell migration even under hypoxia condition, supported by the finding of suppressed expression of Akt and FAK phosphorylation. In this study, gene transduction and Dox induction did not affect cell proliferation. These findings suggest that the gene modulation of phosphorylation sites in PTEN might give a new therapeutic strategy to regulate metastasis in lung cancer.
- © 2011 ERS
