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Transformation of Ba/F3 cells and Rat-1 cells by ETV6/ARG

Oncogene volume 21, pages 4374–4383 (2002)Cite this article

Abstract

ETV6/ARG, a novel fusion gene composed of the ETV6 HLH oligomerization domain and most of sequences of the ARG protein tyrosine, was recently identified in human leukemia cells. The presence of the ETV6/ARG translocation raises the possibility that the resulting fusion protein functions as an oncogene. However, the transforming activity of the ETV6/ARG protein has not been determined and its contribution to leukemogenesis is therefore unknown. Here we address this question by analysing the oncogenic activity of ETV6/ARG in hematopoietic and fibroblast cells. It is demonstrated that expression of ETV6/ARG confers IL3-independent growth to Ba/F3 cells and anchorage independent growth to Rat-1 fibroblasts. It is also shown that multiple signaling molecules, including PI3K, SHC, ras-GAP and CRK-L, are tyrosine phosphorylated in Ba/F3 cells that express ETV6/ARG. Analysis of four different types of ETV6/ARG transcripts previously identified in the AML-M3 leukemia cell line HT93A suggest that ETV6 HLH domain is required for oncogenic activity. Based upon these results it is concluded that ARG can be activated as an oncogene in human malignancy and that the ETV6/ARG oncoprotein triggers some of the same signaling pathways associated with activated ABL oncogenes.

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Acknowledgements

This work is supported by Grants-in-Aids for Scientific Research from the Ministry of Eduction, Science and Culture, Japan (No.12671016) to Y Sakaki, by Grant-in-Aid for Scientific Research (C) No. 13671073 Research Grant from Welfide Medicinal Research Foundation to K Okuda, and by NIH grant CA57273 to GD Kruh.

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Authors and Affiliations

  1. Division of Molecular Cytogenetics, Department of Clinical Pathology, Research Institute, International Medical Center of Japan, Tokyo, 162-0052, Japan

    Yoshimi Iijima, Nguyen Khanh Tri & Yuko Sato

  2. Department of Hygiene, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan

    Keiko Okuda

  3. Division of Molecular Therapy, Advanced Clinical Research Center Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

    Arinobu Tojo, Misao Setoyama & Shigetaka Asano

  4. Laboratory of Functional Genomics, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

    Yoshiyuki Sakaki

  5. Department of Human Genetics, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, 113-0033, Japan

    Nguyen Khanh Tri & Katsushi Tokunaga

  6. Medical Sciences Division, Fox Chase Cancer Center, Philadelphia, 19111, Pennsylvania, PA, USA

    Gary D Kruh

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  1. Yoshimi Iijima
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  9. Gary D Kruh
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Correspondence to Yuko Sato.

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Iijima, Y., Okuda, K., Tojo, A. et al. Transformation of Ba/F3 cells and Rat-1 cells by ETV6/ARG. Oncogene 21, 4374–4383 (2002). https://doi.org/10.1038/sj.onc.1205544

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