Inhibition Of14-3-3ε Expression In SGC7901Gastric Cancer Cells And Its Significance

AIM:The highly conserved14-3-3s protein family has risen to a position of importance in cell biology owing to its involvement in mitogenic and cell survival signaling, cell cycle control and apoptotic cell death.14-3-3ε is found to have an impact on various kind of tumor development. The aim of this study is to investigate the function of14-3-3ε in gastric carcinoma cells and the involved mechanism.METHODS:Short hairpin RNA which aimed at downregulating14-3-3ε was transfected into SGC7901cells. Resistant clones were obtained through puromycin selection. Western blotting was used to detect14-3-3ε expression in transfected cells.The growth of transfected cells was investigated by MTT proliferation assays and the cell cycle by flow cytometer.The effects of14-3-3ε were tested in vivo using allografts in nude mice.The cell cycle related proteins cyclin E and p27were also detected by Western Blotting.RESULTS:We got two cell lines(shRNA1and shRNA2) whose14-3-3ε were obviously down regulated compared with parental SGC7901cells and a cell line (vector) whose14-3-3s expression was not significantly different from parental SGC7901cells. Down-regulation of 14-3-3e by shRNA in SGC7901cells decreased cell proliferation and resulted in G1-S arrest. Further more,14-3-3ε down-regulation caused decreased carcinogenesis in vivo. Consistent with these results, we found that the down-regulation of14-3-3e was correlated with increased p27protein expression and decreased cyclin E expression. Our study showed for the first time that14-3-3e is a positive regulator of growth in gastric cancer.CONCLUSION:14-3-3ε acts as an oncongene in gastric cancer cells by involving cyclin E and p27kip1. Down-regulation of14-3-3ε in SGC7901gastric cancer cells results in inhibition of cell proliferation, G1-S arrest and in vivo decreased carcinogenesis.