This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yang, H. Articles by Lee, M.-H. Search for Related Content PubMed PubMed Citation Articles by Yang, H. Articles by Lee, M.-H.

¹ Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center and Programs in ² Cancer Biology and ³ Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas

Requests for reprints: Mong-Hong Lee, The University of Texas M.D. Anderson Cancer Center, Box 79, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-794-1323; Fax: 713-792-6059. E-mail: mhlee{at}mdanderson.org

The 14-3-3 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 14-3-3 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 inhibits oncogene-activated tumorigenicity. In the present study, we investigated the tumor-suppressive role of 14-3-3 in NPC cells. We found that there is a failure to up-regulate 14-3-3 in response to DNA damage in two NPC cell lines that have p53 mutation. We also found that 14-3-3 interacted with protein kinase B/Akt and negatively regulated the activity of Akt. Overexpression of 14-3-3 inhibited NPC cell growth and blocks DNA synthesis. Overexpression of 14-3-3 also led to inhibition of anchorage-independent growth of NPC cells. In addition, we found that 14-3-3 sensitized NPC cells to apoptosis induced by the chemotherapeutic agent 2-methoxyestradiol. Overexpression of 14-3-3 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 in NPC and suggest that approaches that modulate 14-3-3 activity may be useful in the treatment of NPC. [Mol Cancer Ther 2006;5(2):253–60]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: M-H. Lee is a recipient of the Flemin and Davenport Research Award. The current address for H. Yang is Department of Pathophysiology, Zhongshan University, Guangzhou, China.

⁴ H.Y. Yang, et al. DNA damage-induced protein 14-3-3 inhibits PKB/Akt activation and suppresses Akt-activated cancer, Cancer Research, in press.

Received 9/30/05; revised 11/ 4/05; accepted 12/ 1/05.