Research on mechanisms of multistep tumorigenesis by TLS-CHOP chimeric oncoprotein and its clinical application

• Project/Area Number: 25460480
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Wakayama Medical University
• Principal Investigator: OIKAWA KOSUKE 和歌山県立医科大学, 医学部, 講師 (70348803)
• Co-Investigator(Kenkyū-buntansha): MURAGAKI Yasuteru 和歌山県立医科大学, 医学部, 教授 (40190904)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: キメラ遺伝子 / 粘液型脂肪肉腫 / 発がん機構

Outline of Final Research Achievements

The TLS-CHOP gene specifically seen in myxoid liposarcoma is a chimeric oncogene that is derived from chromosomal translocation. The gene product functions as a transcription factor, and is thought to be involved in tumorigenesis and tumor cell growth. Its detailed molecular mechanism is, however, still unclear. Previous studies have shown that TLS-CHOP induces expression of a transforming-related protein DOL54 and represses expression of an anti-tumor cytokine IL-24. In this study, we have revealed that overrexpression of DOL54 represses IL-24 expression, contributing to maintenance of tumor cell growth. Furthermore, we have identified several molecules related to growth of myxoid liposarcoma cells, and are investigating their molecular functions now at present.

Research Products

• [Journal Article] Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression. (2015)
  • Author(s): Sun Y, Nakanishi M, Sato F, Oikawa K, Muragaki Y, Zhou G.
  • Journal Title: BBRC Volume: 456 Issue: 3 Pages: 721-726
  • DOI: 10.1016/j.bbrc.2014.12.039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Elevated serum 1,25(OH)2-vitamin D3 level attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in kl/kl mice. (2014)
  • Author(s): Sun Y, Zhou G, Gui T, Shimokado A, Nakanishi M, Oikawa K, Sato F, Muragaki Y.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 6563-6563
  • DOI: 10.1038/srep06563
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Smad3 plays an inhibitory role in phosphate-induced vascular smooth muscle cell calcification. (2014)
  • Author(s): A. Shimokado, Y. Sun, M. Nakanishi, F. Sato, K. Oikawa, T. Akasaka, Y. Muragaki.
  • Journal Title: Experimental and Molecular Pathology Volume: 97 Issue: 3 Pages: 458-464
  • DOI: 10.1016/j.yexmp.2014.10.005
  • Peer Reviewed
• [Presentation] 甲状腺癌細胞株に対するマイクロ波効果－誘導された未知なる細胞の検討－. (2015)
  • Author(s): 尾崎 敬, 田伏克惇, 渡邊雄也, 南條佐輝子, 張 穎哲, 中西雅子, 佐藤冬樹, 及川恒輔, 覚道健一, 村垣泰光.
  • Organizer: 第43回和歌山悪性腫瘍研究会
  • Place of Presentation: 日本赤十字和歌山医療センター
  • Year and Date: 2015-12-19
• [Presentation] 粘液型脂肪肉腫特異的キメラ遺伝子TLS-CHOPに制御される新規分子メカニズムの検討. (2015)
  • Author(s): 及川恒輔, 田中正視, 尾崎 敬, 黒田雅彦, 村垣泰光.
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会大会合同大会(BMB2015)
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Identification of novel molecular pathways required for the growth of TLS-CHOP-expressing myxoid liposarcoma cells. (2015)
  • Author(s): Kosuke Oikawa, Masakatsu Takanashi, Fuyuki Sato, Masahiko Kuroda, Yasuteru Muragaki.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] BHLH transcription factor DEC2 negatively regulates TWIST1 and VEGF under hypoxia. (2015)
  • Author(s): Fuyuki Sato, Ujjal Bhawal, Kosuke Oikawa, Yasuteru Muragaki
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 粘液型脂肪肉腫特異的キメラがんタンパクTLS-CHOPの下流分子の検討. (2014)
  • Author(s): 及川恒輔、田中正視、高梨正勝、尾崎 敬、黒田雅彦、村垣泰光.
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Analysis of a novel molecular pathway induced by TLS-CHOP for myxoid liposarcoma tumorigenesis and tumor progression. (2014)
  • Author(s): Kosuke Oikawa, Masakatsu Takanashi, Masako Nakanishi, Fuyuki Sato, Masahiko Kuroda, Yasuteru Muragaki.
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] MAGED2 plays important roles in tumor cell survival. (2014)
  • Author(s): Fuyuki Sato, Kosuke Oikawa, Yasuteru Muragaki, Yanping Zhang.
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 甲状腺未分化癌細胞株に対する非熱的マイクロ波効果の検討. (2014)
  • Author(s): 尾崎敬，田伏克惇，渡邊雄也, 孫 玉静，下角あい子，中西雅子, 佐藤冬樹，及川恒輔，覚道健一，村垣泰光.
  • Organizer: 第33回Microwave Surgery 研究会
  • Place of Presentation: たかつき京都ホテル(大阪府高槻市)
  • Year and Date: 2014-09-11 – 2014-09-12
• [Presentation] 子宮頸癌関連タンパクWAPLによるエピジェネティック制御への関与. (2014)
  • Author(s): 及川恒輔、丹羽麻也子、水崎杏奈、孫 玉静、中西雅子、佐藤冬樹、尾崎 敬、村垣泰光.
  • Organizer: 第82回和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県和歌山市)
  • Year and Date: 2014-07-06
• [Presentation] BHLH型転写因子DEC1の膵癌におけるEMT機能. (2014)
  • Author(s): 佐藤冬樹、中西雅子、及川恒輔、村垣泰光.
  • Organizer: 第82回和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県和歌山市)
  • Year and Date: 2014-07-06
• [Presentation] 甲状腺は再生する臓器か？－マウス動物実験から検討－ (2013)
  • Author(s): 尾崎 敬，覚道健一，伊藤俊治，及川恒輔，村垣泰光，木村芝生子.
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 仙台
• [Presentation] 甲状腺癌細胞株に対する非熱的マイクロ波効果の検討 (2013)
  • Author(s): 尾崎 敬，覚道健一，Gui Ting，Sun Yujing，下角あい子，伊藤俊治，及川恒輔，田伏克惇，村垣泰光.
  • Organizer: 日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] マイクロ波効果－基礎的研究－ 甲状腺癌細胞株に対する非熱的マイクロ波効果の検討 (2013)
  • Author(s): 尾崎 敬，田伏克惇，孫 玉静，下角あい子，伊藤俊治，及川恒輔，覚道健一，村垣泰光.
  • Organizer: Microwave Surgery研究会
  • Place of Presentation: 東京
• [Presentation] Novel molecular pathways in TLS-CHOP-dependent mechanism for myxoid liposarcoma tumorigenesis and tumor progression (2013)
  • Author(s): Kosuke Oikawa, Masakatsu Takanashi, Masahiko Kuroda, Yasuteru Muragaki.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 粘液型脂肪肉腫特異的キメラがんタンパクTLS-CHOPによる多段階発がん機構の検討 (2013)
  • Author(s): 及川恒輔, 伊藤俊治, 田中正視, 高梨正勝, 孫 玉静, 尾崎 敬, 黒田雅彦, 村垣泰光.
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 粘液型脂肪肉腫特異的キメラがんタンパクTLS-CHOPによる発がん分子メカニズム
  • Author(s): 及川恒輔, 伊藤俊治, 孫 玉静, 下角あい子, 尾崎 敬, 村垣泰光.
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山
• [Presentation] 甲状腺癌細胞株に対する非熱的マイクロ波効果の検討
  • Author(s): 尾崎 敬, Sun Yujing, 下角あい子, 伊藤俊治, 及川恒輔, 村垣泰光, 田伏克惇, 覚道健一.
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山