2003 Fiscal Year Final Research Report Summary
Molecular analysis of aberrant signal transduction of membrane receptors as a basis for diagnosis and treatment of malignant lymphomas
| Project/Area Number |
14370067
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
WATANABE Toshiki The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (30182934)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Takaomi The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (80293447)
HORIE Ryouichi Kitasato University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80229228)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Hodgkin's Lymphoma / ALCL / CD30 / NF-kB / NPM-ALK / HTLV-1 / ATL / DNA methylation |
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| Research Abstract |
(1)Hodgkin's lymphoma and anaplastic large cell lymphomas (ALCL) : We demonstrated that the constitutive activation of NF-kB results from "ligand-independent activation" of overexpressed CD30 on the Hodgkin/Reed-Sternberg (H-RS)cells, and that inhibition of CD30 signaling by transduction of a dominat negative decoy CD30 that lacks the cytoplasmic region induced apoptotic cell death of H-RS cells (Horie et al., Oncogene 21,2493,2002). We shoed that cytoplasmic aggregation of TRAF2 and TRAF5 proteins represents constant signaling of CD30 (Horie et al., Am J Pathol 160,1647,2002). We demonstrated that the AP-1 binding sequence located near the microsatellite counteracts the suppressive effects of the microsatellite on the CD30 promoter activity (Watanabe et al., Am J Pathol 163,633,2003). We showed that p80NPM-ALK inhibits ligand-independent signal transduction by overexpressed CD30 in ALCL cells though sequestration of TRAF proteins in the complex of NPM-ALK and wild type NPM (Horie et al., Cancer Cell 5,353,2004).
(2)ATL :
We demonstrated that GSK-3b-b-catenin-TCF/LEF pathway is a possible downstream target of the constitutively activated PKCbll in ATL cells.
Expression profile analysis of ATL cells identified 67 genes as specifically overexpressed ones in ATL cells, 44 in activated T-cells of PBMC of HTLV-1 carriers, 24 in HTLV-1 infected cell lines.
We revealed 5'-LTR specific CpG heavy methylation of HTLV-1 provirus in ATL cells and infected T-cells in peripheral blood of symptomatic carriers, which may be one base for latent infection of HTLV-1 (Koiwa et al., J Virol 76,9389,2002).
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[Journal Article] Ligand-independent signaling by overexpressed CD30 drives NF-κB activation in Hodgkin-Reed Sternberg cells.2002
Author(s)
Horie R, Watanabe T, Morishita Y, Ito K, Ishida T, Kanegae Y, Saito I, Higashihara M, Mori S, Kadin ME, Watanabe T.
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Journal Title
Oncogene 21
Pages: 2493-2503
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis2002
Author(s)
Satoh M, Toma H, Sugahara K, Etoh K, Shiroma Y, Kiyuna S, Takara M, Matsuoka M, Yamaguchi K, Nakada K, Fujita K, Kojima S, Hori E, Kamihira S, Sato Y, Tanaka Y, Watanabe T.
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Journal Title
Oncogene 21
Pages: 2466-2475
Description
「研究成果報告書概要(欧文)」より
