14-3-3σ mediates G2-M arrest produced by 5-aza-2′-deoxycytidine and possesses a tumor suppressor role in endometrial carcinoma cells

Objectives. To determine the effect of 5-aza-2'-deoxycytidine (DAC) on human endometrial carcinoma cell (HECC) oncogenicity and demonstrate a molecular mechanism by which DAC modulates HECC oncogenicity. Methods. The effect of DAC was tested on HECC RL95-2, AN3, Ishikawa and ECC1 cells. The role of 14-3-3 sigma on HECC oncogenicity in response to DAC treatment was evaluated in RL95-2 and AN3 cells after forced expression or silencing of 14-3-3 sigma gene expression. Results. Treatment of HECC with DAC produced non-cytotoxic cell growth inhibition and G2/M cell cycle arrest. This effect was strongly correlated with increased expression of p21 and 14-3-3 sigma. Silencing of 14-3-3 sigma induced cellular proliferation and reduced the effect of DAC on cell cycle arrest in G2/M phases. Conversely, forced expression of 14-3-3 sigma showed the opposite effect. Furthermore, forced expression of 14-3-3 sigma in human endometrial cell lines reduced cell growth and colony formation. Conclusions. We suggest that 14-3-3 sigma in HECC suppresses cell proliferation and mediates DAC induced G2/M arrest and inhibition of cell proliferation in HECC. (C) 2012 Elsevier Inc. All rights reserved.