Down Regulation of FOXO1 Promotes Cell Proliferation in Cervical Cancer

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2013.04.24; Accepted: 2013.07.09; Published: 2014.08.22 The Forkhead transcription factor FOXO1, an important downstream target of phosphatidylinosi-tol-3-kinase (PI3K)/AKT signaling pathway, regulates cellular homeostasis by maintaining cell prolifer-ation, apoptosis and viability in normal cells. Though, the function and regulation of FOXO1 is well documented in many cancers, the molecular mechanism of its regulation in cervical cancer is largely unknown. In the present study we have investigated the role of PI3K inhibition on FOXO1 regulation. Expression profiling of primary tumors and cell lines show over expression of PIK3CA and AKT1; and down regulation of FOXO1. Lack of FOXO1 promoter methylation and inability of hypomethylating drug 5-Aza-2’-deoxycytidine and HDAC inhibitor trichostatin A to reactivate FOXO1 expression suggest that loss of FOXO1 expression is due to mechanisms other than promoter methyla-tion/acetylation. Inhibition of PI3K by LY294002 decreased the level of p-AKT1 and activated FOXO