14-3-3sigma, a p53 regulator, suppresses tumor growth of nasopharyngeal carcinoma
Abstract
The 14-3-3sigma gene product, up-regulated 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 14-3-3sigma interacts with p53 in response to DNA damage and stabilizes the expression of p53. In addition, we also showed that overexpression of 14-3-3sigma inhibits oncogene-activated tumorigenicity. In the present study, we investigated the tumor-suppressive role of 14-3-3sigma in NPC cells. We found that there is a failure to up-regulate 14-3-3sigma in response to DNA damage in two NPC cell lines that have p53 mutation. We also found that 14-3-3sigma interacted with protein kinase B/Akt and negatively regulated the activity of Akt. Overexpression of 14-3-3sigma inhibited NPC cell growth and blocks DNA synthesis. Overexpression of 14-3-3sigma also led to inhibition of anchorage-independent growth of NPC cells. In addition, we found that 14-3-3sigma sensitized NPC cells to apoptosis induced by the chemotherapeutic agent 2-methoxyestradiol. Overexpression of 14-3-3sigma in both NPC cell line...Continue Reading
References
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