Identification of downstream regulatory factor in RET signaling pathway and its application to cancer treatment

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Chubu University
• Principal Investigator: ICHIHARA Masatoshi Chubu University, 生命健康科学部, 教授 (00314013)
• Co-Investigator(Kenkyū-buntansha): IWAMOTO Takashi 中部大学, 生命健康科学部, 教授 (60223426) ; QIAO Shanlou 中部大学, 生命健康科学部, 准教授 (00343658) ; MURAKUMO Yoshiki 名古屋大学, 大学院・医学系研究科, 准教授 (40324438)
• Project Period (FY): 2008 – 2010
• Keywords: RET / チロシンキナーゼ / アイソフォーム / DNAマイクロアレイ

Research Abstract

Ret tyrosine kinase (RET) plays critical roles in embryonic development as well as oncogenesis. RET is mainly expressed as two isoforms, RET51 and RET9, which have different C-terminal ends generated through alternative splicing , whereas previous studies show that RET9 is indispensable for nephrogenesis and enteric neurogenesis. We found remarkable increase of tyrosine- phosphorylated proteins in the cells after inducible expression of RET9 in MEF3T3 cells. We demonstrated that 261 genes were differentially expressed under inducible expression of either RET51 or RET9 by gene expression profiling. Ingenuity pathway analysis revealed that gene expression-related genes, including transcription factors, were enriched in these differentially expressed genes. Next we tried to identify differentially binding protein to RET between RET51 and RET9 using LC/MS, but we failed to find such candidate proteins, accounting for different function between RET51 and RET9.

Research Products

• [Journal Article] Assessment of factors influencing FDG uptake in non-small cell lung cancer on PET/CT by investigating histological differences in expression of glucose transporters 1 and 3 and tumour size. (2011)
  • Author(s): Suzawa N, Ito M, Qiao S, Uchida K, Takao M, Yamada T, Takeda K, Murashima S
  • Journal Title: Lung Cancer. 72 Pages: 191-198
  • Peer Reviewed
• [Journal Article] beta-Catenin signaling regulates the timing of cell differentiation in mouse retinal progenitor cells. (2011)
  • Author(s): Ouchi Y, Baba Y, Koso H, Taketo MM, Iwamoto T, Aburatani H, Watanabe S
  • Journal Title: Mol Cell Neurosci. 46 Pages: 770-780
  • Peer Reviewed
• [Journal Article] The molecular chaperone Hsp90 regulates accumulation of DNA polymerase eta at replication stalling sites in UV-irradiated cells. (2010)
  • Author(s): Sekimoto T, Oda T, Pozo FM, Murakumo Y, Masutani C, Hanaoka F, Yamashita T
  • Journal Title: Mol Cell. 37 Pages: 79-89
  • Peer Reviewed
• [Journal Article] ATRA inhibits ceramide kinase transcription in a human neuroblastoma cell line, SH-SY5Y cells : the role of COUP-TFI. (2010)
  • Author(s): Murakami M, Ito H, Hagiwara K, Yoshida K, Sobue S, Ichihara M, Takagi A, Kojima T, Tanaka K, Tamiya-Koizumi K, Kyogashima M, Suzuki M, Banno Y, Nozawa Y, Murate T
  • Journal Title: J Neurochem. 112 Pages: 511-520
  • Peer Reviewed
• [Journal Article] REGgamma modulates p53 activity by regulating its cellular localization. (2010)
  • Author(s): Liu J, Yu G, Zhao Y, Zhao D, Wang Y, Wang L, Li L, Zeng Y, Dang Y, Wang C, Gao G, Long W, Lonard DM, Qiao S, Tsai MJ, Zhang B, Luo H, Li X
  • Journal Title: J Cell Sci. 123 Pages: 4076-4084
  • Peer Reviewed
• [Journal Article] Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells. (2010)
  • Author(s): Kurotsuchi A, Murakumo Y, Jijiwa M, Kurokawa K, Itoh Y, Kodama Y, Kato T, Enomoto A, Asai N, Terasaki H, Takahashi M
  • Journal Title: Cancer Sci. 101 Pages: 1147-1155
  • Peer Reviewed
• [Journal Article] Processing of CD109 by furin and its role in the regulation of TGF-beta signaling. (2010)
  • Author(s): Hagiwara S, Murakumo Y, Mii S, Shigetomi T, Yamamoto N, Furue H, Ueda M, Takahashi M
  • Journal Title: Oncogene. 29 Pages: 2181-2191
  • Peer Reviewed
• [Journal Article] Modulation of microRNA processing by p53. (2009)
  • Author(s): Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K
  • Journal Title: Nature. 460 Pages: 529-533
  • Peer Reviewed
• [Journal Article] Increased expression of glial cell line-derived neurotrophic factor and neurturin in a case of colon adenocarcinoma associated with diffuse ganglioneuromatosis. (2009)
  • Author(s): Qiao S, Iwashita T, Ichihara M, Murakumo Y, Yamaguchi A, Isogai M, Sakata K, Takahashi M
  • Journal Title: Clin Neuropathol. 28 Pages: 105-112
  • Peer Reviewed
• [Journal Article] Requirement of DHCR24 for postnatal development of epidermis and hair follicles in mice. (2009)
  • Author(s): Mirza R, Qiao S, Murata Y, Seo H
  • Journal Title: Am J Dermatopathol. 31 Pages: 446-452
  • Peer Reviewed
• [Journal Article] Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress. (2009)
  • Author(s): Kato T, Shimono Y, Hasegawa M, Jijiwa M, Enomoto A, Asai N, Murakumo Y, Takahashi M
  • Journal Title: Cancer Res. 69 Pages: 3597-3604
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• [Journal Article] Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. (2009)
  • Author(s): Itoh T, Fujita Y, Ito M, Masuda A, Ohno K, Ichihara M, Kojima T, Nozawa Y
  • Journal Title: Biochem Biophys Res Commun. 389 Pages: 651-656
  • Peer Reviewed
• [Journal Article] A role for AP-1 in matrix metalloproteinase production and invadopodia formation of v-Crk-transformed cells. (2009)
  • Author(s): Hasegawa H, Senga T, Ito S, Iwamoto T, Hamaguchi M
  • Journal Title: Exp Cell Res. 315 Pages: 1384-1392
  • Peer Reviewed
• [Journal Article] Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease. (2009)
  • Author(s): Fu Y, Ito M, Fujita Y, Ichihara M, Masuda A, Suzuki Y, Maesawa S, Kajita Y, Hirayama M, Ohsawa I, Ohta S, Ohno K
  • Journal Title: Neurosci Lett. 453 Pages: 81-85
  • Peer Reviewed
• [Journal Article] Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus. (2009)
  • Author(s): Enomoto A, Asai N, Namba T, Wang Y, Kato T, Tanaka M, Tatsumi H, Taya S, Tsuboi D, Kuroda K, Kaneko N, Sawamoto K, Miyamoto R, Jijiwa M, Murakumo Y, Sokabe M, Seki T, Kaibuchi K, Takahashi M
  • Journal Title: Neuron. 63 Pages: 774-787
  • Peer Reviewed
• [Journal Article] Establishment of cells to monitor Microprocessor through fusion genes of microRNA and GFP. (2008)
  • Author(s): Tsutsui M, Hasegawa H, Adachi K, Miyata M, Huang P, Ishiguro N, Hamaguchi M, Iwamoto T
  • Journal Title: Biochem Biophys Res Commun. 372 Pages: 856-861
  • Peer Reviewed
• [Journal Article] A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1. (2008)
  • Author(s): Suzuki C, Murakumo Y, Kawase Y, Sato T, Morinaga T, Fukuda N, Enomoto A, Ichihara M, Takahashi M
  • Journal Title: Biochem Biophys Res Commun. 366 Pages: 226-232
  • Peer Reviewed
• [Journal Article] Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice. (2008)
  • Author(s): Hasegawa T, Enomoto A, Kato T, Kawai K, Miyamoto R, Jijiwa M, Ichihara M, Ishida M, Asai N, Murakumo Y, Ohara K, Niwa Y, Goto H, Takahashi M
  • Journal Title: Oncogene. 27 Pages: 5684-5695
  • Peer Reviewed
• [Presentation] 水素水投与後の血中・臓器濃度と肝臓内酸化ストレス軽減効果の検討 (2010)
  • Author(s): 市原正智、祖父江沙矢加、山井一晃、大桑哲男
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] Cereulide毒素による肝障害に対する分子状水素の肝保護効果の検討 (2010)
  • Author(s): 祖父江沙矢加、岡本陽、安形則雄、市原正智
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] Zebrafishを用いたRNA結合タンパク質Lin28の機能解析 (2010)
  • Author(s): 山本純矢、大内靖夫、岩本隆司
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] 腸管上皮細胞におけるRNA結合分子Lin28の機能解析 (2010)
  • Author(s): 大内靖夫、朝枝祐太、水野麻衣、高岡祐司、岩本隆司
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] Role of CD109 in the regulation of TGF-beta signaling. (2010)
  • Author(s): Yoshiki Murakumo, Sumitaka Hagiwara, Shinji Mii, Minako Hagikura, Masahide Takahashi
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] CD109-LacZノックインマウスにおける皮膚表現型の解析 (2010)
  • Author(s): 三井伸二、村雲芳樹、浅井直也、高橋雅英
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] 転写因子TFII-IとhREV7との相互作用とその生理学的意義の解析 (2010)
  • Author(s): 村雲芳樹、高橋雅英
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] 分子状水素によるI型アレルギー抑制機構の解明 (2010)
  • Author(s): 伊藤智広、藤田泰典、伊藤美佳子、増田章男、市原正智、小島俊男、野澤義則、大野欽司、伊藤雅史
  • Organizer: 日本基礎老化学会第33回大会
  • Place of Presentation: 名古屋
  • Year and Date: 20100617-20100618
• [Presentation] ヒト神経膠芽腫細胞におけるCD109発現の生物学的意義の検討 (2010)
  • Author(s): 村雲芳樹、高橋雅英
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20100427-20100429
• [Presentation] CD109 expression promotes cell activity and enhances EGF signaling in human glioblastoma cells. (2010)
  • Author(s): Murakumo Y, Zhang JM, Takahashi M
  • Organizer: 101th Annual Meeting, American association for Cancer Research.
  • Place of Presentation: Washington D.C., USA
  • Year and Date: 20100417-20100421
• [Presentation] 分子状水素によるI型アレルギー抑制の分子機構 (2010)
  • Author(s): 伊藤智広、藤田泰典、伊藤美佳子、増田章男、市原正智、小島俊男、野澤義則、大野欽司、伊藤雅史
  • Organizer: 第130回日本薬学会
  • Place of Presentation: 岡山
  • Year and Date: 20100328-20100330
• [Presentation] 水素水投与後の血中水素濃度動態の検討 (2010)
  • Author(s): 山井一晃、祖父江沙矢加、大桑哲男、市原正智
  • Organizer: 第2回水素研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-02-12
• [Presentation] ヒト神経膠芽腫細胞におけるCD109発現の生物学的意義の検討 (2009)
  • Author(s): 村雲芳樹、萩原純孝、高橋雅英
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] v-SrcによるSPHK1 mRNA安定化と発現増強 (2008)
  • Author(s): 祖父江沙矢加、村上真史、坂野喜子、伊藤裕美、高四強、古畑彩子、高木明、小嶋哲人、野澤義則、村手隆、市原正智
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 20081209-20081212
• [Presentation] 口腔癌におけるCD109の発現 (2008)
  • Author(s): 萩原純孝、村雲芳樹、重富俊雄、光藤健司、藤内祝、上田実、高橋雅英
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081028-20081030
• [Presentation] 基底細胞型乳癌の新しいマーカーとてのCD109 (2008)
  • Author(s): 長谷川正規、森谷鈴子、三井伸二、佐藤朋子、時々輪真由美、村雲芳樹、市原周、高橋雅英
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20080515-20080517