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Human T-cell leukemia virus type 1 Tax protein induces the expression of STAT1 and STAT5 genes in T-cells

Oncogene volume 18, pages 2667–2675 (1999)Cite this article

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) Tax transforms normal T-cells in the presence of interleukin (IL)-2 in vitro. STAT is a family of transcription factors that play a pivotal role in cytokine-induced functions of a various type of cells. We investigated the involvement of STATs in the transformation of T-cells by HTLV-1. HTLV-1-transformed T-cell lines expressed higher amounts of STAT1, STAT3 and STAT5 RNA and proteins than virus-negative T cells. The expression of STAT1 and STAT5 in a human T-cell line was induced by Tax. IL-2 induced the DNA binding activity of STAT3 and STAT5 of a HTLV-1-transformed cell line and then stimulated its proliferation. In contrast, IL-2 did neither in a cell line lacking STAT3 and STAT5. The expression of STAT1, STAT3 and STAT5 mRNAs were also induced by a T-cell mitogen in normal human peripheral blood mononuclear cells. Our results suggest that the induction of STAT1 and STAT5 by Tax enhances cytokine-induced functions of virus-infected T-cells, hence the induction may play a role in IL-2-dependent transformation steps of T-cells by HTLV-1.

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Acknowledgements

We thank Drs J Ihle and K Yamamoto for the STAT plasmids, Dr M Nakamura for JPX-9 cells and Drs Y Tanaka, S Ruscetti and R Fisher for providing anti-Tax and anti-STAT3 antibodies, respectively. We also thank Drs M Nakamura, K Yamamoto, A Miyajima and T Kimura for their valuable discussion and comments. This work was supported in part by a Grant-in Aid for Cancer Research, from the Ministry of Education, Science, Sports and Culture of Japan, and CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation.

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Authors and Affiliations

  1. Department of Microbiology, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113, Japan

    Naomi Nakamura, Masaaki Arai & Naoki Yamamoto

  2. Department of Immunotherapeutics, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113, Japan

    Naomi Nakamura, Masahiro Fujii, Tomonori Tsukahara, Masaaki Arai, Takashi Ohashi & Mari Kannagi

  3. Helix Research Institute, Kisarazu, 292, Chiba, Japan

    Hiroshi Wakao

  4. Department of Virology, Niigata University School of Medicine, Asahimachi-Dori, 951-8510, Niigata, Japan

    Masahiro Fujii

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  1. Naomi Nakamura
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Nakamura, N., Fujii, M., Tsukahara, T. et al. Human T-cell leukemia virus type 1 Tax protein induces the expression of STAT1 and STAT5 genes in T-cells. Oncogene 18, 2667–2675 (1999). https://doi.org/10.1038/sj.onc.1202608

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