Analysis of molecular basis for occurance of Hodgkin lympnoma and anaplastic large cell lymphoma

• Project/Area Number: 18590345
• 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, School of Medicine, Associate Prof. (80229228)
• Co-Investigator(Kenkyū-buntansha): HIGASHIHARA Masaaki Kitasato University, School of Medicine, Prof (80165084) ; WATANABE Toshiki University of Tokyo, Graduate School of Frontier Sciences, Prof (30182934)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Hodgkin lymphoma / anaplastic large cell lymphoma / NF-κB / NPM-ALK / P80 / JunB / NF-kB

Research Abstract

High expression of CD30 and JunB is characteristic of tumor cells in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). The possible inter-relationships of CD30 and JunB were examined in this study. We found that the CD30 promoter in tumor cells of both nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) positive and NPM-ALK negative ALCL and HL is regulated by a constitutively active CD30-extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK). Phosphorylated ERK1/2 MAPK was confirmed in nuclei of tumor cells in biopsies of ALCL and HL. CD30-ERK1/2 MAPK signals induce JunB expression which maintains high activity of the CD30 promoter. JunB induction appears to be largely independent of NF-KB in ALCL and HL. These results demonstrate a common mechanism of CD30 overexpression in ALCL and HL although the results of CD30 signaling differ between NPM- ALK positive ALCL and other subgroups ; NPM-ALK negative ALCL, cutaneous ALCL and HL as we recently reported.

Research Products

• [Journal Article] Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation inmice inoculated with tax-deficient adult T-cell leukemia-derived cell lines (2007)
  • Author(s): Ohsugi T, 4名, Horie R, 2名
  • Journal Title: Cancer Lett 257 Pages: 206-215
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] TRAF activation of C/EBPb (NF-IL6) via p38 MAPK induces HIV-1 gene expre ssion in monocvtes/macrophages (2007)
  • Author(s): Horie R, 8名
  • Journal Title: Microbes Infect 48 Pages: 721-728
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] IkBalpa independent induction of NF-kappaB and its inhibition by DHMEQ in Hodgkin-Reed-Stemberg cells (2007)
  • Author(s): Watanabe M, 10名, Horie R
  • Journal Title: Lab Invest 87 Pages: 372-382
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Dehydroxymethylepoxyquinomicin(DHMEQ)therapy reduces tumor formation in mice inoculated with tax-deficient adult T-cell leukemia-derived cell lines (2007)
  • Author(s): Ohsugi, T, Kumasaka, T, Okada, S, Ishida, T, Yamaguchi, K, Horie, R, Watanabe, T, Umezawa, K
  • Journal Title: Cancer Lett 257(2) Pages: 206-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] TRAF activation of C/EBPb (NF-IL6) via p38 MAPK induces HIV-1 gene expression in monocytes/macrophages (2007)
  • Author(s): Horie, R, Ishida, T, Maruyama-Nagai, M, Ito, K, Watanabe, M, Yoneyama, A, Higashihara, M, Kimura, S, Watanabe, T
  • Journal Title: Microbes Infect 48 Pages: 721-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IkBalpa independent induction of NF-kappaB and its inhibition b DHMEQ in Hodgkin-Reed-Sternberg cells (2007)
  • Author(s): Watanabe, M, Dewan, MZ, Taira, M, Shoda, M, Honda, M, Sata, T, Higashihara, M, Kadin, ME, Watanabe, T, Yamamoto, N, Umezawa, K, Horie, R
  • Journal Title: Lab Invest 87 Pages: 372-82
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dehydroxymethylepoxyquinomicin(DHMEQ)therapy reduces tumor formation in mice inoculated with tax-deficient adult T-cell leukemia-derived cell lines. (2007)
  • Author(s): Ohsugi T, 4名, Horie R, 2名
  • Journal Title: Cancer Lett. 257 Pages: 206-215
  • Peer Reviewed
• [Journal Article] TRAF activation of C/EBPb(NF-IL6)via p38 MAPK induces HIV-1 gene expression in monocytes/macrophages. (2007)
  • Author(s): Horie R, 8名
  • Journal Title: Microbes Infect. 48 Pages: 721-728
  • Peer Reviewed
• [Journal Article] IkBalpa independent induction of NF-kappaB and its inhibition by DHMEQ in Hodgkin-Reed-Sternberg cells. (2007)
  • Author(s): Watanabe M, 10名, Horie R
  • Journal Title: Lab Invest. 87 Pages: 372-382
  • Peer Reviewed
• [Journal Article] DHMEQ,a new NF-kappaB inhibitor,induces apoptosis and enhances fludarabine effects on chronic lymphocytic leukemia cells (2006)
  • Author(s): HorieR, 他9名
  • Journal Title: Leukemia 20(5) Pages: 800-6
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Blocking NF-kappaB as a potential strategy to treat adult T-cell leukemia/lymphoma (2006)
  • Author(s): Hone R, Watanabe T, Umezawa K.
  • Journal Title: Drug News Perspect 19(4) Pages: 201-9
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Transactivation of the ICAM-1 gene by CD30 in Hodgkin's lymphoma (2006)
  • Author(s): Uchihara JN-4名-Horie R, 他4名
  • Journal Title: Int J Cancer 118(5) Pages: 1098-107
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] In vitro and in vivo antitumor activity of the NF-kappaB inhibitor DHMEQ in the human cell leukemia virus type I-infected cell line,HUT-102 (2006)
  • Author(s): Ohsugi T-3名-Horie R, 他3名
  • Journal Title: Leuk Res 30(1) Pages: 90-7
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] DHMEQ, a new NF-kappaB inhibitor, induces apoptosis and enhances fludarabine effects on chronic lymphocytic leukemia cells (2006)
  • Author(s): Horie, R, Watanabe, M, Okamura, T, Taira, M, Shoda, M, Motoji, T, Utsunomiya, A, Watanabe, T, Higashihara, M, Umezawa, K
  • Journal Title: Leukemia 20 Pages: 800-806
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Blocking NF-kappaB as a potential strategy to treat adult T-cell leukemia/lymphoma (2006)
  • Author(s): Horie, R, Watanabe, T, Umezawa, K
  • Journal Title: Drug News Perspect Pages: 201-209
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transactivation of the ICAM-1 gene by CD30 in Hodgkin's lymphoma (2006)
  • Author(s): Uchihara, JN, Matsuda, T, Okudaira, T, Ishikawa, C, Masuda, M, Rorie, R, Watanabe, T, Ohta, T, Takasu, N, Mori, N
  • Journal Title: Int J Cancer 118 Pages: 1098-1107
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vitro and in vivo antitumor activity of the NF-kappaB inhibitor DHMEQ in the human T-cell leukemia virus type I-infected cell line, HUT-102 (2006)
  • Author(s): Ohsugi, T, Kumasaka, T, Ishida, A, Ishida, T, Rorie, R, Watanabe, T, Umezawa, K, Yamaguchi, K
  • Journal Title: Leuk Res 30 Pages: 90-97
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DHMEQ, a new NF-kappaB inhibitor, induces apoptosis and enhances fludarabine effects on chronic lvmnhocvtic leukemia cells. (2006)
  • Author(s): Horie R 他9名
  • Journal Title: Leukemia 20(5) Pages: 800-6
• [Journal Article] Blocking NF-kappaB as a potential strategy to treat adult T-cell leukemia/lymphoma. (2006)
  • Author(s): Horie R, Watanabe T, Umezawa K
  • Journal Title: Drug News Perspect 19(4) Pages: 201-9
• [Journal Article] Transactivation of the ICAM-1 gene by CD30 in Hodgkin's lymphoma. (2006)
  • Author(s): Uchihara JN-4名, Horie R 他4名
  • Journal Title: Int J Cancer. 118(5) Pages: 1098-107
• [Journal Article] In vitro and in vivo antitumor activity of the NF-kappaB inhibitor DHMEQ in the human T-cell leukemia virus type I-infected cell line, HUT-102. (2006)
  • Author(s): Ohsugi T-3名-, Horie R 他3名
  • Journal Title: Leuk Res. 30(1) Pages: 90-7
• [Presentation] 変異型IkBaを有するH-RS細胞でのIkBbを介したNF-kB誘導とDHMEQによる分子標的療法 (2007)
  • Author(s): 堀江 良一, 他8名
  • Organizer: 第49回日本臨床血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Targeting of constitutive NF-KB activation in transformed and untransformed HTLV-1-infected T cells by DHMEQ : A strategy for chemoprevention and therapy of adult T-cell leukemia. Int J Mol. Med (2006)
  • Author(s): R., Horie
  • Organizer: The 11th world Congress on Advances in Oncology, 9 th International Symposium on Molecular Medicine
  • Place of Presentation: Hersonissos, Crete, Greece
  • Description: 「研究成果報告書概要(欧文)」より