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Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis

Oncogene volume 24, pages 1122–1127 (2005)Cite this article

Abstract

Aurora kinases are known to play a key role in maintaining mitotic fidelity, and overexpression of aurora kinases has been noted in various tumors. Overexpression of aurora kinase activity is thought to promote cancer development through a loss of centrosome or chromosome number integrity. Here we observed augmentation of G12V-mutated HRAS-induced neoplastic transformation in BALB/c 3T3 A31-1-1 cells transfected with Aurora-A. Aurora-A-short hairpin RNA (shRNA) experiments showed that the expression level of Aurora-A determines susceptibility to transformation. Aurora-A gene amplification was noted in human patients with tongue or gingival squamous carcinoma (4/11). Amplification was observed even in pathologically normal epithelial tissue taken at sites distant from the tumors in two patients with tongue cancer. However, overexpression of Aurora-A mRNA was observed only within the tumors of all patients examined (11/11). Our data indicate that Aurora-A gene amplification and overexpression play a role in human carcinogenesis, largely due to the effect of Aurora-A on oncogenic cell growth, rather than a loss of maintenance of centrosomal or chromosomal integrity.

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Acknowledgements

We thank Yasuhiko Terada for his valuable suggestions. We would also like to thank Fumio Suzuki for his administrative support. MT is supported by REIMEI Research Resources (Grants H12-040 and H15-030) from the Japan Atomic Energy Research Institute.

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Authors and Affiliations

  1. Department of Regulatory Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Masaaki Tatsuka, Shiho Suto & Hidehiko Kawai

  2. Dental School, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Sunao Sato, Shojiro Kitajima, Mutsumi Miyauchi & Takashi Takata

  3. Dental Hospital, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Ikuko Ogawa & Takashi Takata

  4. Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Ishikawa, 920-0293, Japan

    Masayo Maeda & Takahide Ota

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  1. Masaaki Tatsuka
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  2. Sunao Sato
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  3. Shojiro Kitajima
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Correspondence to Masaaki Tatsuka.

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Tatsuka, M., Sato, S., Kitajima, S. et al. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene 24, 1122–1127 (2005). https://doi.org/10.1038/sj.onc.1208293

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