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The 14-3-3 sigma gene product, upregulated by p53 in response to DNA damage, is involved in cell-cycle checkpoint control and is a human cancer epithelial marker down-regulated in various tumors. However, its role and function have not been established in nasopharyngeal carcinoma (NPC), a tumor of epithelial origin. Recently, we found that 14-3-3 sigma interacts with p53 in response to DNA damage and stabilizes the expression of p53. In addition, we also showed that overexpression of 14-3-3 sigma inhibits oncogene-activated tumorigenicity. In the present study, we investigated the tumor suppressive role of 14-3-3 sigma in NPC cells. We found that 14-3-3 sigma was not properly upregulated by p53 in response to DNA damage in two non-isogenic NPC cell lines. We also found that 14-3-3 sigma interacted with protein kinase B (PKB)/Akt and negatively regulated the activity of Akt. Overexpression of 14-3-3 sigma inhibited NPC cell growth and blocks DNA synthesis. 14-3-3 sigma overexpression also led to inhibition of anchorage-independent growth of NPC cells. In addition, we found that 14-3-3 sigma sensitized NPC cells to apoptosis induced by the chemotherapeutic agent 2-Methoxyestradiol. 14-3-3 sigma overexpression in both NPC cell lines reduced the tumor volume in nude mice, which could have significance for clinical application. These findings provide an insight into the roles of 14-3-3 sigma in NPC and suggest that approaches that modulate 14-3-3 sigma activity may be useful in the treatment of NPC.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]