Analysis of mature B cell lymphomagenes by mutated epigenetic factors

• Project/Area Number: 25860245
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Keio University
• Principal Investigator: SUGIHARA Eiji 慶應義塾大学, 医学部, 特任助教 (50464996)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: リンパ腫 / エピジェネィクス / c-Myc / Ezh2 / MEF2B / マウスモデル / エピジェネティクス / 非ホジキンリンパ腫 / バーキットリンパ腫

Outline of Final Research Achievements

It has been suggested that deregulation of gene transcription by epigenetic abnormality contributes to tumorigenesis. In this study, we focused on the histone modification-regulated factors Ezh2 and MEF2B whose gene mutations have been often reported, and studied their roles in mature B cell lymphomagenesis. Although mutated Ezh2 enhanced the tri-methylation of histone H3K27, exogenously expression of mutated Ezh2 in germinal center B cells did not induce lymphoma in transplanted mice. MEF2B also showed similar results. On the other hands, c-Myc, frequently overexpressed in lymphoma, could directly induce mature B cell lymphoma. Therefore, mutated histone modification-regulated factors are not direct drivers in lymphomagenesis but probably contribute to the promotion of lymphoma.

Research Products

• [Journal Article] Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells. (2014)
  • Author(s): Hosonaga M, Arima Y, Sugihara E, Kohno N and Saya H
  • Journal Title: Cancer Sci Volume: 105 Issue: 7 Pages: 779-787
  • DOI: 10.1111/cas.12427
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IGF2 Preserves Osteosarcoma Cell Survival by Creating an Autophagic State of Dormancy That Protects Cells against Chemotherapeutic Stress (2014)
  • Author(s): Shimizu T, Sugihara E, Yamaguchi-Iwai S, Tamaki S, Koyama Y, Kamel W, Ueki A, Ishikawa T, Chiyoda T, Osuka S, Onishi N, Ikeda H, Kamei J, Matsuo K, Fukuchi Y, Nagai T, Toguchida J, Toyama Y, Muto A, Saya H
  • Journal Title: Cancer Res Volume: 74 Issue: 22 Pages: 6531-6541
  • DOI: 10.1158/0008-5472.can-14-0914
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of leukemic stem cell in acute lymphoblastic leukemia (2014)
  • Author(s): Sugihara E, Inukai T, Saya H.
  • Journal Title: 血液内科 Volume: 69 Pages: 595-601
  • NAID: 40020262491
• [Journal Article] Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. (2014)
  • Author(s): Nobusue H
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 3368-3368
  • DOI: 10.1038/ncomms4368
  • Peer Reviewed
• [Journal Article] IGF1 receptor signaling regulates adaptive radioprotection in glioma stemcells (2013)
  • Author(s): Osuka S. Sampetrean O, Shimizu T, Saga l, Onishi N, Sugihara E, Okubo J, Fujita S, Takano S, Matsumura A, Saya H
  • Journal Title: Stem Cells Volume: 31 Issue: 4 Pages: 627-640
  • DOI: 10.1002/stem.1328
  • Peer Reviewed
• [Journal Article] The Arf/p53 protein module, which induces apoptosis, down-regulates histone H2AX to allow normal cells to survive in the presence of anti-cancer drugs. (2013)
  • Author(s): Yuko Atsumi, Aki lnase, Eiji Sugihara, Ryo Sakasai, Hiroaki Fujimori, Hirobumi Teraoka, Hideyuki Saya, Masamoto Kanno, Fumio Tashiro, Hitoshi Nakagami, Mitsuko Masutani, Ken-ichi Yoshioka
  • Journal Title: The Journal of Biological Chemistry Volume: 288巻 Issue: 19 Pages: 13269-13277
  • DOI: 10.1074/jbc.m112.402560
  • Peer Reviewed
• [Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells. (2013)
  • Author(s): Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
  • Journal Title: Cancer Sci Volume: (in press) Issue: 7 Pages: 880-888
  • DOI: 10.1111/cas.12163
  • Peer Reviewed
• [Presentation] Characterization of leukemic stem-like cells with drug resistance and plasticity in B-ALL model (2014)
  • Author(s): Sugihara E、Shimizu T, Mogushi K, Hashimoto N, Saya H
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Cancer stem-like cells in mouse B-ALL model show the quiescent state, glycolytic gene expression and plasticity (2013)
  • Author(s): Sugihara E, Shimizu T, Mogushi K, Hashimoto N, Saya H
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Establishment of simple and rapid Burkitt lymphoma model (2013)
  • Author(s): Hashimoto N, Sugihara E, Saya H
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Remarks] 慶應義塾大学 医学部 先端医科学研究所 遺伝子制御研究部門
  • URL: http://genereg.jp/index.html
• [Remarks] 慶應義塾大学 医学部 先端医科学研究所 遺伝子制御研究部門 ホームページ
  • URL: http://genereg.jp/index.html