Molecular mechanisms of Hodgkin and anaplastic large cell lymhoma triggered by CD30 induction and P80

• Project/Area Number: 20590374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kitasato University
• Principal Investigator: HORIE Ryouichi Kitasato University, 医学部, 准教授 (80229228)
• Co-Investigator(Kenkyū-buntansha): IGASHIHARA Masaaki 北里大学, 医学部, 教授 (80165084)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: CD30 / JunB / Ets-1 / NPM-ALK / ポジキンリンパ腫 / 未分化大細胞型リンパ腫 / NPM-Alk / Hodgkinリンパ腫 / 未分化大細胞性リンパ腫 / Hodkinリンパ腫

Research Abstract

Overexpression of CD30 and JunB is a hallmark of tumor cells in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). We report that CD30-ERK-MAPK signaling induces JunB, which maintains constitutive activation of the hypomethylated CD30 promoter. We also localize a cis-acting enhancer in the JunB promoter by Ets-1. We show that Ets-1 enhances JunB promoter activation dependent on CD30 or the NPM-ALK-ERK 1/2 MAPK pathway.

Research Products

• [Journal Article] The side population, as a precursor of Hodgkin and Reed-Sternberg cells and a target for nuclear factor-kappaB inhibitors in Hodgkin's lymphoma. (2010)
  • Author(s): Nakashima M, Ishii Y, Watanabe M, Togano T, Umezawa K, Higashihara M, Watanabe T, Horie R.
  • Journal Title: Cancer Sci. 101 Pages: 2490-2496
  • Peer Reviewed
• [Journal Article] Inhibition of active HIV-1 replication by NF-kappaB inhibitor DHMEQ. (2010)
  • Author(s): Miyake A, Ishida T, Yamagishi M, Hara T, Umezawa K, Watanabe T, Horie R.
  • Journal Title: Microbes Infect. 12 Pages: 400-408
  • Peer Reviewed
• [Journal Article] CD3- and CD4-positive plasmablastic lymphoma: a literature review of JapanesePlasmablastic, lymphoma cases. (2010)
  • Author(s): Suzuki Y, Yoshida T, Nakamura N, Kamata H, Kotani S, Ohsaka M, Kajita S, Miyazaki K, Ohtani S, Nakayama M, Horie R, Hayakawa K, Niitsu N, Higashihara M.
  • Journal Title: Intern Med. 49 Pages: 1801-1805
  • Peer Reviewed
• [Journal Article] A case of giardiasis expressing severe systemic symptoms and marked, hypereosinophilia. (2010)
  • Author(s): Suzuki Y, Nakamura T, Tokoro M, Togano T, Ohsaka M, Kohri M, Hirata Y, Miyazaki K, Danbara M, Horie R, Miura I, Sunakawa K, Higashihara M.
  • Journal Title: Parasitol Int. 59 Pages: 487-489
  • NAID: 10029825838
  • Peer Reviewed
• [Journal Article] Constitutive activity of nuclear transcription factor kappaB is observed in follicular lymphoma. (2010)
  • Author(s): Suzuki Y, Yoshida T, Horie R, Tsuruta T, Togano T, Ohsaka M, Miyazaki K, Danbara M, Ohtani S, Okayasu I, Higashihara M.
  • Journal Title: J Clin Exp Hematop. 50 Pages: 45-50
  • Peer Reviewed
• [Journal Article] The side population, as a precursor of Hodgkin and Reed-Sternberg cells and a target for nuclear factor-kB inhibitors in Hodgkin's lymphoma. (2010)
  • Author(s): Nakashima M(6名) Horie R
  • Journal Title: Cancer Sci. Volume: 101 Pages: 2490-2496
  • Peer Reviewed
• [Journal Article] CD3- and CD4-positive plasmablastic lymphoma : a literature review of Japanese Plasmablastic lymphoma cases. (2010)
  • Author(s): Suzuki Y(10名)Horie R(3名)
  • Journal Title: Intern Med. Volume: 49 Pages: 1801-1805
  • NAID: 130000299647
  • Peer Reviewed
• [Journal Article] Constitutive activity of nuclear transcription factor kappaB is observed in follicular lymphoma. (2010)
  • Author(s): Suzuki Y(1名)Horie R(8名)
  • Journal Title: J Clin Exp Hematop. Volume: 50 Pages: 45-50
  • Peer Reviewed
• [Journal Article] Inhibition of active HIV-1 replication by NF-kappaB inhibitor DHMEQ. (2010)
  • Author(s): Miyake A, (3名), Horie R
  • Journal Title: Microbes and Infection (in press, [Epub ahead of print])
  • Peer Reviewed
• [Journal Article] Induction of oncogene addiction shift to NF-kB by camptothecin in solid tumor cells. (2009)
  • Author(s): Togano T, Sasaki M, Watanabe M, Makoto Nakashima M, Tsuruo T, Umezawa K, Higashihara M, Toshiki Watanabe T, Horie R.
  • Journal Title: Biochem Biophys Res Commun. 390 Pages: 60-64
  • Peer Reviewed
• [Journal Article] Transient inhibition of NF-kappaB by DHMEQ induces cell death of primary effusion lymphoma without HHV-8 reactivation. (2009)
  • Author(s): Dabaghmanesh N, Matsubara A, Miyake A, Nakano K, Ishida T, Katano H, Horie R, Umezawa K, Watanabe T.
  • Journal Title: Cancer Sci. 100 Pages: 737-746
  • Peer Reviewed
• [Journal Article] CD20-positive T-cell large granular lymphocyte leukemia: case report and review of the literature. (2009)
  • Author(s): Miyazaki K, Ohsaka M, Suzuki Y, Danbara M, Horie R, Higashihara M.
  • Journal Title: Intern Med. 48 Pages: 1443-1447
  • NAID: 130000122030
  • Peer Reviewed
• [Journal Article] Lymphoproliferative disorders after immunosuppressive therapy for aplastic anemia: a case report and literature review. (2009)
  • Author(s): Suzuki Y, Niitsu N, Hayama M, Katayama T, Ishii R, Osaka M, Miyazaki K, Danbara M, Horie R, Yoshida T, Nakamura N, Higashihara M.
  • Journal Title: Acta Haematol. 121 Pages: 21-26
  • Peer Reviewed
• [Journal Article] Induction of oncogene addiction shift to NF-kB by camptothecin in solid tumor cells. (2009)
  • Author(s): Togano T, (7名), Horie R
  • Journal Title: Biochem Biophys Res Commun 390 Pages: 60-64
  • Peer Reviewed
• [Journal Article] Transient inhibition of NF-kappaB by DHMEQ induces cell death of primary effusion lymphoma without HHV-8 reactivation. (2009)
  • Author(s): Dabaghmanesh N, (5名), Horie R, (1名), Watanabe T
  • Journal Title: Cancer Sci. 100 Pages: 737-746
  • Peer Reviewed
• [Journal Article] Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic large cell lymphoma. (2008)
  • Author(s): Watanabe M, Ogawa Y, Itoh K, Koiwa T, Kadin ME, Watanabe T, Okayasu I, Higashihara M, Horie R.
  • Journal Title: Lab Invest. 88 Pages: 48-57
  • Peer Reviewed
• [Journal Article] Identification of the RelA domain responsible for action of a new NF-kappaB inhibitor DHMEQ. (2008)
  • Author(s): Watanabe M, Nakashima M, Togano T, Higashihara M, Watanabe T, Umezawa K, Horie R.
  • Journal Title: Biochem Biophys Res Commun. 376 Pages: 310-314
  • Peer Reviewed
• [Journal Article] Induction of apoptosis in Epstein-Barr virus-infected B-lymphocytes by the NF-?B inhibitor DHMEQ. (2008)
  • Author(s): Miyake A, Dewan MZ, Ishida T, Watanabe M, Honda M, Sata T, Yamamoto N, Umezawa K, Watanabe T, Horie R.
  • Journal Title: Microbes Infect. 10 Pages: 748-56
  • Peer Reviewed
• [Journal Article] Inactivation of NF-kappaB components by covalent binding of (-)-dehydroxymethylepoxyquinomicin to specific cysteine residues. (2008)
  • Author(s): Yamamoto M, Horie R, Takeiri M, Kozawa I, Umezawa K.
  • Journal Title: J Med Chem. 51 Pages: 5780-5788
  • Peer Reviewed
• [Journal Article] Identification of the RelA domain responsible for action of a new NF-kappaB inhibitor DHMEQ. (2008)
  • Author(s): Watanabe M, (5名), Horie R.
  • Journal Title: Biochem Biophys Res Commun. 376 Pages: 310-314
  • Peer Reviewed
• [Journal Article] Inactivation of NF-kappaB components by covalent binding of (-)-dehydroxymethylepoxyquinomicin to specific cysteine residues. (2008)
  • Author(s): Yamamoto M, Horie R, (5名).
  • Journal Title: J Med Chem. 51 Pages: 5780-5788
  • Peer Reviewed
• [Journal Article] Induction of apoptosis in Epstein-Barr virus-infected B-lymphocyteby the NF-κB inhibitor DHMEQ. (2008)
  • Author(s): Miyake A, (5名), Horie R.
  • Journal Title: Microbes Infect. 10 Pages: 748-756
  • Peer Reviewed
• [Presentation] Affect of aberrant T cell antigenexpression on DLBCL patients'background and prognosis. (2010)
  • Author(s): Suzuki Y.,(13名)Horie R, Higashihara M
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Affect of aberrant T cell antigen expewssion on DLBCL patients'backgrownd and prognosis (2010)
  • Author(s): Suzuki Y(13名)Horie R, Higashihara M
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-25
• [Presentation] Identification of the RelA domainresponsible for the action of a newNF-kB inhibitor DHMEQ (2009)
  • Author(s): RyouichiHorie, (3名)Masaaki Higashihara, Toshiki Watanabe, Kazuo Umezawa
  • Organizer: 第71回日本血液学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] NF-kB阻害剤DHMEQの標的分子と核への分布を阻害するドメインの同定 (2009)
  • Author(s): 堀江良一, (他6名)
  • Organizer: 第13回日本がん分子標的治療研究会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2009-06-26
• [Presentation] CD30プロモーターメチル化とJunBを介したCD30誘導機構の解析 (2008)
  • Author(s): 堀江良一、(7名)東原正明
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] CD30プロモーターメチル化とJunBを介したCD30誘導機構の解析 (2008)
  • Author(s): 堀江良一, 他7名
  • Organizer: 日本血液学会総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2008-10-12
• [Presentation] 難治性リンパ系悪性腫瘍におけるNF一κBシグナル伝達への阻害剤の応用 (2008)
  • Author(s): 堀江良一
  • Organizer: 第12回がん分子標的治療学会シンポジウム招待講演
  • Place of Presentation: 東京
  • Year and Date: 2008-06-28
• [Book] 悪性リンパ腫の基礎と臨床 (2011)
  • Author(s): 堀江良一, 他
  • Total Pages: 538
  • Publisher: 医薬ジャーナル社
• [Book] みんなに役立つ悪性リンパ腫の基礎と臨床(リンパ腫 微小環境)(押味和夫編)
  • Author(s): 堀江良一
  • Publisher: 医薬ジャーナル社
• [Book] 病理診断に役立っ分子生物学(臨時増刊号29)(金井弥栄、石川俊平、池田栄一編)(病理 と臨床)
  • Author(s): 堀江良一
  • Publisher: 文光堂