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Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance
Article first published online: 18 NOV 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 9, pages 1864–1873, 1 May 2011
How to Cite
Park, H. R., Kim, S.-H., Lee, S. Y., Sung, J. M., Park, A. R., Kang, S., Kim, B. G., Choi, Y. P., Kim, Y.-B. and Cho, N. H. (2011), Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance. Cancer, 117: 1864–1873. doi: 10.1002/cncr.25760
- Issue published online: 19 APR 2011
- Article first published online: 18 NOV 2010
- Manuscript Accepted: 1 OCT 2010
- Manuscript Revised: 20 SEP 2010
- Manuscript Received: 23 JUN 2010
Vol. 117, Issue 12, 2825, Article first published online: 29 DEC 2010
- nuclear localization;
- radiation resistance;
- head and neck squamous cell carcinoma;
Although radiation resistance is a primary issue in radiation therapy, attempts to find predictors of radiation resistance have met with little success. The authors therefore aimed to determine predictors for radiation resistance to improve the prognosis of head and neck squamous cell carcinoma (HNSCC).
HNSCC cell lines, SCC15, SCC25, and QLL1, irradiated with an acute dose of 4 grays (Gy) (RR-4), a cumulative dose of 60 Gy (RR-60), and a booster dose of 4 Gy over 60 Gy (RR-60 + 4), were used with nonirradiated cell lines. Those were used in cDNA microarray, proteomics, Western blotting, and immunofluorescence, respectively. One hundred five HNSCC tissue samples with radiation resistance were analyzed by immunohistochemistry.
Western blot analysis of RR-60 cell lines was identical to the data of Nm23-H1 overexpression by cDNA array and proteomic screening. Immunofluorescence demonstrated significant nuclear translocation of Nm23-H1 in RR-4 and RR-60 cell lines, and less but still intense nuclear shuttling in RR-60 + 4. Similarly, Nm23-H1 nuclear localization was observed in 20% (21 of 105) of tissue samples. Univariate analysis demonstrated that Nm23-H1 nuclear localization was strongly associated with overall and recurrence-free survival. Multivariate stepwise Cox regression analysis showed that Nm23-H1 nuclear localization (odds ratio [OR], 7.48) and N stage (OR, 2.13) were associated with overall survival, and Nm23-H1 nuclear localization (OR, 3.02), T stage (OR, 1.43), and insufficient tumor margin (OR, 3.27) were associated with recurrence-free survival.