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The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

Notch receptors play an essential role in cellular processes during embryonic and postnatal development, including maintenance of stem cell self-renewal, proliferation, and determination of cell fate and apoptosis. Deregulation of Notch signaling has been implicated in some genetic diseases and tumorigenesis. The function of Notch signaling in a variety of tumors can be either oncogenic or tumor-suppressive, depending on the cellular context. In this study, Notch1 overexpression was observed in the majority of 45 astrocytic gliomas with different grades and in U251MG glioma cells. Transfection of siRNA targeting Notch1 into U251 cells in vitro downregulated Notch1 expression, associated with inhibition of cell growth, arrest of cell cycle, reduction of cell invasiveness, and induction of cell apoptosis. Meanwhile, tumor growth was delayed in established subcutaneous gliomas in nude mice treated with Notch1 siRNA in vivo. These results suggest that Notch1 plays an important oncogenic role in the development and progression of astrocytic gliomas. Furthermore, knockdown of Notch1 expression by siRNA simultaneously downregulated the expression of EGFR and the important components of its downstream pathways, including PI3K, p-AKT, K-Ras, cyclin D1 and MMP9, indicating the crosstalk and interaction of Notch and EGFR signaling pathways.

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Acknowledgements

This work is supported by National Natural Science Foundation of China (30300365), Tianjin Science and Technology Committee (06YFSZSF01100).

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Authors and Affiliations

  1. Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, People’s Republic of China

    Peng Xu, Mingzhe Qiu, Zhiyong Zhang, Chunsheng Kang, Rongcai Jiang, Zhifan Jia, Guangxiu Wang & Peiyu Pu

  2. Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, 300052, People’s Republic of China

    Peng Xu, Mingzhe Qiu, Zhiyong Zhang, Chunsheng Kang, Rongcai Jiang, Zhifan Jia, Guangxiu Wang & Peiyu Pu

  3. Department of Neurology, Henry Ford Hospital, Detroit, MI, 48202, USA

    Hao Jiang

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  1. Peng Xu
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Correspondence to Peiyu Pu.

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Peng Xu and Mingzhe Qiu contributed equally to this work.

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Xu, P., Qiu, M., Zhang, Z. et al. The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo. J Neurooncol 97, 41–51 (2010). https://doi.org/10.1007/s11060-009-0007-1

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  • DOI: https://doi.org/10.1007/s11060-009-0007-1

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