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  • Oncogenomics
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Transformation of vascular endothelial cells by a point mutation in the Tie2 gene from human intramuscular haemangioma

Oncogene volume 23, pages 8700–8704 (2004)Cite this article

Abstract

Tie2, an endothelial-cell-specific receptor tyrosine kinase, collaborates with vascular endothelial growth factor (VEGF) in regulating angiogenesis and vascular maturation. Here, we report a mutation of glycine to aspartic acid at the second glycine of the GXGXXG motif of Tie2 (G833DTie2) in human intramuscular haemangiomas (IMHs) of the capillary type. Murine endothelial cells (ECs) overexpressing this G833DTie2 receptor exhibited an increase in cell proliferation at low serum concentrations and angiosarcomas developed in nude mice, whereas cells overexpressing either wild-type Tie2 or Q837HTie2 failed to elicit these responses. Furthermore, the G833DTie2 receptor increased VEGF expression in ECs. These findings provide molecular mechanisms for pathogenesis of IMH.

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Acknowledgements

We thank Drs Yu-Tian Peng, Zhong-Hua Zhou, Zhong-Ming Jiang, and Xiao-Gang Xu of Shanghai Changhai Hospital for patient data and Yasufumi Sato of Tohoku University for the murine EC line. We thank Professor Norihiko Maeda and Professor Takata Takashi of Hiroshima University for helpful discussions. This work was supported in part by grants from the Shanghai Changhai Hospital for the Promotion of Medical Science to HW, by a Grant-in-Aid for Young Scientists (A) from the ministry of Education, Science, Sport and Culture of Japan to YZ, and by a Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science and by a grant from Smoking Research Foundation to TO.

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Authors and Affiliations

  1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, 734-8553, Japan

    Hua Wang, Yan Zhang, Shigeaki Toratani & Tetsuji Okamoto

  2. Department of Oral Medicine and Maxillofacial Surgery, Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China

    Hua Wang

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  1. Hua Wang
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  2. Yan Zhang
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Correspondence to Tetsuji Okamoto.

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Wang, H., Zhang, Y., Toratani, S. et al. Transformation of vascular endothelial cells by a point mutation in the Tie2 gene from human intramuscular haemangioma. Oncogene 23, 8700–8704 (2004). https://doi.org/10.1038/sj.onc.1208006

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