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14-3-3σ, a p53 regulator, suppresses tumor growth of nasopharyngeal carcinoma
Ist Teil von
Molecular cancer therapeutics, 2006-02, Vol.5 (2), p.253-260
Ort / Verlag
American Association for Cancer Research
Erscheinungsjahr
2006
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
The 14-3-3σ 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 14-3-3σ interacts with p53 in response to DNA damage
and stabilizes the expression of p53. In addition, we also showed that overexpression of 14-3-3σ inhibits oncogene-activated
tumorigenicity. In the present study, we investigated the tumor-suppressive role of 14-3-3σ in NPC cells. We found that there
is a failure to up-regulate 14-3-3σ in response to DNA damage in two NPC cell lines that have p53 mutation. We also found
that 14-3-3σ interacted with protein kinase B/Akt and negatively regulated the activity of Akt. Overexpression of 14-3-3σ
inhibited NPC cell growth and blocks DNA synthesis. Overexpression of 14-3-3σ also led to inhibition of anchorage-independent
growth of NPC cells. In addition, we found that 14-3-3σ sensitized NPC cells to apoptosis induced by the chemotherapeutic
agent 2-methoxyestradiol. Overexpression of 14-3-3σ 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 14-3-3σ in NPC and suggest
that approaches that modulate 14-3-3σ activity may be useful in the treatment of NPC. [Mol Cancer Ther 2006;5(2):253–60]