Basic research for investigation of novel oncogenic mechanism by TLS-CHOP chimeric oncoprotein and its clinical application

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• 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): 2010 – 2012
• Keywords: 腫瘍 / キメラ遺伝子

Research Abstract

The TLS-CHOP fusion gene derived from chromosomal translocation is myxoid liposarcoma-specific oncogene. However, its oncogenesis mechanism and functions in tumor cells are still unclear. In this study, we have revealed that TLS-CHOP represses an anticancer cytokine MDA-7/IL-24 expression, and represses miR-486 that targets a tumor cell growth and metastasis activator PAI-1 In addition, a novel molecular pathway that induces expression of a tumorigenesis-related protein PRG4 has been suggested.

Research Products

• [Journal Article] TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis regulator PAI-1 in human myxoid liposarcoma (2012)
  • Author(s): N. Borjigin, S. Ohno, W. Wu, M. Tanaka, R. Suzuki, K. Fujita, M. Takanashi, K. Oikawa, T. Goto, T. Motoi, T. Kosaka, K. Yamamoto, M. Kuroda
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 427 Pages: 355-360
  • DOI: DOI:10.1016/j.bbrc.2012.09.063
  • Peer Reviewed
• [Journal Article] MicroRNAs that target Ca2+ transporters are involved in vascular smooth muscle cell calcification (2012)
  • Author(s): T. Gui, G. Zhou, Y. Sun, A. Shimokado, S. Itoh, K. Oikawa, Y. Muragaki
  • Journal Title: Lab. Invest Volume: 92 Pages: 1250-1259
  • DOI: DOI:10.1038/labinvest.2012.85
  • Peer Reviewed
• [Journal Article] A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression (2012)
  • Author(s): K. Oikawa, M. Tanaka, S. Itoh, M. Takanashi, T. Ozaki, Y. Muragaki, M. Kuroda
  • Journal Title: Br. J. Cancer Volume: 106 Pages: 1976-1979
  • DOI: DOI:10.1038/bjc.2012.199
  • Peer Reviewed
• [Journal Article] Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen (2012)
  • Author(s): M.Xu,M,Takanashi,K.Oikawa,H.Nishi,K.Isaka,T.Yoshimoto,J.Uhyashiki,M.Kuroda
  • Journal Title: Cancer Sci. Volume: 103 Pages: 821-827
  • DOI: DOI:10.1111/j.1349-7006.2012.02221.x.
  • Peer Reviewed
• [Journal Article] Fibulin-5 Protein is reduced in the lung of patients with spontaneous pneumothorax who are under 25 years old (2012)
  • Author(s): Y. Hirai, Y. Muragaki, S. Itoh, K. Oikawa, M. Juri, T. Kondo, Y. Okamura
  • Journal Title: Ann. Thorac. Cardiovasc. Surg Volume: 18 Pages: 200-205
  • DOI: DOI:org/10.5761/atcs.oa.11.01758.
  • Peer Reviewed
• [Journal Article] Aberrant expression of the P2 promoter-specific transcript Runx1 in epiphyseal cartilage of Trps1-null mice (2011)
  • Author(s): S. Kanno, T. Gui, S. Itoh, Z. Gai, Y. S u n , K. Oikawa, M. Yoshida, Y. Muragaki
  • Journal Title: Exp. Mol. Pathol Volume: 90 Pages: 143-148
  • DOI: DOI:10.1016/j.yexmp.2010.11.010.
  • Peer Reviewed
• [Journal Article] Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing (2011)
  • Author(s): M. Kawakatsu, S. Kanno, T. G u i, Z. Gai, S. Itoh, H. Tanishima, K. Oikawa, Y. Muragaki
  • Journal Title: Exp. Mol. Pathol Volume: 90 Pages: 107-115
  • DOI: DOI:10.1016/j.yexmp.2010.10.011
  • Peer Reviewed
• [Journal Article] SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo (2010)
  • Author(s): R. Nishioka, S. Itoh, T. Gui, Z. G a i , K. Oikawa, M. Kawai, M. Tani, H. Yamaue, Y. Muragaki
  • Journal Title: Exp. Mol. Pathol Volume: 89 Pages: 1 4 9-157
  • Peer Reviewed
• [Journal Article] Trps1 haploinsufficiency promotes renal fibrosis by increasing Arkadia expression (2010)
  • Author(s): Z. Gai, G. Zhou, T. Gui, S. Itoh, K. Oikawa, K. Uetani, Y. Muragaki
  • Journal Title: J. Am. Soc. Nephrol Volume: 21 Pages: 1468-1476
  • DOI: DOI:10.1681/ASN.2009121201
  • Peer Reviewed
• [Journal Article] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development (2010)
  • Author(s): M. Shigoka, A. Tsuchida, T. Matsudo , Y. Nagakawa, H. Saito, Y. Suzuki, T. Aoki, Y. Murakami, H. Toyoda, T. Kumada, R. Bartenschlager, N. Kato, M. Ikeda, T. Takashina, M. Tanaka, R. Suzuki, K. Oikawa, M. Takanashi, M. Kuroda
  • Journal Title: Pathol. Int Volume: 60 Pages: 351-357
  • DOI: DOI:10.1111/j.1440-1827.2010.02526.x.
  • Peer Reviewed
• [Presentation] Wapl regulates HP1 expression and levels of various histone H3 tail modifications (2012)
  • Author(s): 及川恒輔
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: マリンメッセ福岡(福岡県)
  • Year and Date: 2012-12-12
• [Presentation] 粘液型脂肪肉腫特異的キメラがんタンパクTLS-CHOPが関わる多段階発がん機構の探究 (2012)
  • Author(s): 及川恒輔
  • Organizer: 和歌山悪性腫瘍研究会
  • Place of Presentation: 和歌山ビッグ愛(和歌山県)
  • Year and Date: 2012-10-15
• [Presentation] TLS-CHOP represses expression of the antitumor cytokine MDA-7/IL24 in myxoid liposarcoma (2012)
  • Author(s): 及川恒輔
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: さっぽろ芸文館(北海道)
  • Year and Date: 2012-09-20
• [Presentation] A novel oncogenic mechanism of the chimeric oncoprotein TLS-CHOP mediated by a tumor suppressor protein MDA-7/IL24 (2011)
  • Author(s): 及川恒輔
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-14
• [Presentation] Expression of PRG4 variant C specifically functions in tumor formation and development of myxoid liposarcoma (2011)
  • Author(s): 孫 玉静
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-14
• [Presentation] Gdf5/Trps1 signaling regulates Prg4 expression in the superficial cells of the articular cartilage (2011)
  • Author(s): 伊藤俊治
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-13
• [Presentation] 粘液型脂肪肉腫における分子治療の可能性を探る (2011)
  • Author(s): 及川恒輔
  • Organizer: 日本バイオセラピィ学会学術集会総会
  • Place of Presentation: ダイワロイネットホテル和歌山
  • Year and Date: 2011-12-01
• [Presentation] Analysis of the novel molecular function of the cohesin-associated protein Wapl (2011)
  • Author(s): 及川恒輔
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-03
• [Presentation] コヒーシン制御タンパクWaplの新しい機能の検討 (2011)
  • Author(s): 及川恒輔
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2011-07-10
• [Presentation] 粘液型脂肪肉腫におけるPRG4の機能の検討 (2011)
  • Author(s): 孫 玉静
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2011-07-10
• [Presentation] 指節間関節形成における軟骨原基表層細胞の役割 (2011)
  • Author(s): 伊藤俊治
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2011-07-10
• [Presentation] カルシウム輸送体をターゲットにするマイクロRNAはリンで誘導される (2011)
  • Author(s): 桂二
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2011-07-10
• [Presentation] The PRG4 variants associated with sarcoma development have a potential to be therapeutic targets (2010)
  • Author(s): 及川恒輔
  • Organizer: 日本分子生物学会年会日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] Gdf5/Trps1は関節形成軟骨細胞の分化を調節する (2010)
  • Author(s): 伊藤俊治
  • Organizer: 日本分子生物学会年会日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] 粘液型脂肪肉腫におけるキメラタンパクTLS-CHOPによる腫瘍化機構の検討 (2010)
  • Author(s): 及川恒輔
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2010-07-11
• [Presentation] Prg4はGdf5/Trps1の支配下に指節間関節形成に関与する (2010)
  • Author(s): 伊藤俊治
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2010-07-11
• [Presentation] 腎発生期における尿管芽の枝分かれと集合管形成の調節分子機構 (2010)
  • Author(s): 蓋 志博
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2010-07-11
• [Presentation] klothoマウスにおける血管石灰化と血中リン濃度との関連性について (2010)
  • Author(s): 桂二
  • Organizer: 和歌山医学会総会
  • Place of Presentation: 和歌山県立医科大学(和歌山県)
  • Year and Date: 2010-07-11