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Targeting fibroblast growth factor receptor 3 enhances radiosensitivity in human squamous cancer cells

Oncogene volume 30, pages 4447–4452 (2011)Cite this article

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Abstract

Conventional therapies including radiation therapy cannot cure squamous cell carcinoma (SCC), and new treatments are clearly required. Our recent studies have shown that SCC cell lines exhibiting radioresistance show significant upregulation of the fibroblast growth factor receptor 3 (FGFR3) gene. We hypothesized that inhibiting FGFR3 would suppress tumor cell radioresistance and provide a new treatment approach for human SCCs. In the present study, we found that RNA interference-mediated FGFR3 depletion in HSC-2 cells, a radioresistant cell line, induced radiosensitivity and inhibited tumor growth. Use of an FGFR3 inhibitor (PD173074) obtained similar results with suppression of the autophosphorylation extracellular signal-regulated kinase pathway in HSC-2 cells and lung cancer cell lines. Moreover, the antitumor growth effect of the combination of PD173074 and radiation in vivo was also greater than that with either drug alone or radiation alone. Our results provided novel information on which to base further mechanistic study of radiosensitization by inhibiting FGFR3 in human SCC cells and for developing strategies to improve outcomes with concurrent radiotherapy.

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Acknowledgements

We thank Lynda C Charters for proofreading this manuscript. This work was supported by a grant-in-aid from the Ministry of Education, Science, Sports and Culture of Japan (no. 22659364), a grant-in-aid from the Japan Society for Promotion of Science Fellows (1952163), a grant-in-aid for Exploratory Research (19659520) and the 21st Century Center of Excellence Programs grant.

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Authors and Affiliations

  1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan

    K Uzawa, T Ishigami, K Fushimi, A Kasamatsu, M Shiiba & H Tanzawa

  2. Division of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan

    K Uzawa, A Kasamatsu, Y Sakamoto, K Ogawara, M Shiiba & H Tanzawa

  3. Department of Radiology, Graduate School of Medicine, Chiba University, Chiba, Japan

    T Kawata & H Ito

  4. Department of Oral and Maxillofacial Surgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

    K Shinozuka & H Bukawa

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  1. K Uzawa
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  2. T Ishigami
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  4. T Kawata
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Correspondence to K Uzawa.

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Uzawa, K., Ishigami, T., Fushimi, K. et al. Targeting fibroblast growth factor receptor 3 enhances radiosensitivity in human squamous cancer cells. Oncogene 30, 4447–4452 (2011). https://doi.org/10.1038/onc.2011.159

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  • DOI: https://doi.org/10.1038/onc.2011.159

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