Alteration of phosphatidylinositol 3-kinase cascade in the multilobulated nuclear formation of adult T cell leukemia/lymphoma (ATLL)

  • Ryu-ichi Fukuda
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Ayako Hayashi
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Atae Utsunomiya
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Yuko Nukada
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Rie Fukui
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Katsuhiko Itoh
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Katsunari Tezuka
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Kazumasa Ohashi
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Kensaku Mizuno
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Manabu Sakamoto
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Masahiro Hamanoue
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...
  • Takashi Tsuji
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, and Tissue Engineering Research Center, Research Institute of Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima 890-0064, Japan; Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Pharmaceutical Research Laboratory, JT Inc., Takatsuki, Osaka 569-1125,...

抄録

<jats:p>Adult T cell leukemia/lymphoma (ATLL) has been characterized as one of the most aggressive human neoplasias and its incidence is thought to be caused by both genetic and epigenetic alterations to the host cellular genes of T cells infected with human T cell leukemia virus type I (HTLV-I). A multilobulated nuclear appearance is an important diagnostic marker of ATLL, and we have now identified that the molecular mechanisms underlying these formations occur through microtubule rearrangement via phosphatidylinositol 3-kinase (PI3-kinase) activation by AILIM/ICOS signaling. We also show that PTEN and/or SHIP-1, which are PIP3 inositol phosphatases that inhibit the activation of downstream effectors of the PI3-kinase cascade, are disrupted in both ATLL neoplasias and in multilobulated nuclei-forming Jurkat cells. This down-regulation of PTEN was found to be essential for the formation of ATLL-type nuclear lobules. Furthermore, PI3-kinase and PTEN activities were observed to be closely associated with cellular proliferation. Thus, our results suggest that alteration of PI3-kinase signaling cascades, as a result of the down-regulation of inositol phosphatases, induces ATLL-type multilobulated nuclear formation and is also associated with the cellular proliferation of malignant T cell leukemias/lymphomas.</jats:p>

収録刊行物

被引用文献 (11)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報

問題の指摘

ページトップへ