• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Annual Research Report

上皮-間質相互作用の解析と分子標的治療

Research Project

Project/Area Number 17016032
Research InstitutionKyoto University

Principal Investigator

武藤 誠  Kyoto University, 医学研究科, 教授 (70281714)

Co-Investigator(Kenkyū-buntansha) 青木 正博  京都大学, 医学研究科, 准教授 (60362464)
三好 弘之  京都大学, 医学研究科, 助教 (30362479)
北村 剛規  京都大学, 医学研究科, 助教 (10378622)
Keywords癌 / マイクロアレイ / シグナル伝達 / 遺伝子改変マウス / MMP7 / Lkb1 / mTORC1
Research Abstract

1.Apc^<Δ716>マウスの良性腺腫と比べると、Apc/Smad4複合変異マウスの腸管に発生する腺癌では著しい間質増生(線維芽細胞の増加と細胞外基質の蓄積)が認められる。前年度までにDNAマイクロアレイを用いてMMP7のmRNAが腺癌で増加することを見いだした。本年度はApc/Smad4複合変異マウスの腺癌では腫瘍上皮細胞で活性型MMP7蛋白質の発現が増加していること、間質増生を促進することが知られているサイトカイン(TGF-β、IGF-I、TNF-αなど)のmRNAの発現は腺腫と腺癌で変わらないことを見いだした。また、腺癌におけるMMP7の発現増加が間質増生に関与する可能性を検討するためMmp7(-/-)マウスとApc/Smad4複合変異マウスを交配しApc/Smad4:Mmp7(-/-)複合変異マウスを作出した(投稿準備中)。
2.Lkb1(+/-)マウスは50週齢以上で肝細胞癌(HCC)を自然発症する。経時的な病理学的観察により、正常肝細胞から前癌病変、HCCへと段階的に癌化が進行することが示唆されているが、Lkb1正常アレルは前癌病変で既に消失しており、HCCへの進行にはさらに別の変化が必要であると考えられた。DNAマイクロアレイ解析により、正常部と比較してHCCで発現の変化した遺伝子群を見いだしたところ、Cd14、Ly6dなど炎症によって誘導される因子の発現が上昇していたことから、Lkb1(+/-)マウスのHCC形成過程における間質反応の役割が示唆された(投稿準備中)。
3.腸管腫瘍形成におけるmTORC1経路の役割を明らかにするためにmTORC1阻害剤であるRAD001をApc^<Δ716>マウスに経口投与したところ、腫瘍の数は40%、大きさは50%減少することが分かった。RAD001投与により腫瘍細胞の増殖率が60%にまで低下したがアポトーシスには変化がなかった。また、一部の新生血管でmTORC1経路が活性化していること、RAD001投与により腫瘍血管新生が30%程抑制されることを明らかにした(投稿中)。

  • Research Products

    (33 results)

All 2008 2007 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (13 results) Remarks (1 results)

  • [Journal Article] Loss of Fgfr2 leads to partial XY sex reversal.2008

    • Author(s)
      Bagheri-Fam S, et. al.
    • Journal Title

      Dev Biol. 314

      Pages: 71-83

    • Peer Reviewed
  • [Journal Article] Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation.2008

    • Author(s)
      Dunty WC Jr, et. al.
    • Journal Title

      Development 135

      Pages: 85-94

    • Peer Reviewed
  • [Journal Article] Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis.2008

    • Author(s)
      Liu F, et. al.
    • Journal Title

      Dev Biol. 313

      Pages: 210-224

    • Peer Reviewed
  • [Journal Article] Keeping out the bad guys: gateway to cellular target therapy.2007

    • Author(s)
      Kitamura T, et. al.
    • Journal Title

      Cancer Res. 67

      Pages: 10099-10102

    • Peer Reviewed
  • [Journal Article] Distinct roles of Wnt/beta-catenin and Bmp signaling during early cardiogenesis.2007

    • Author(s)
      Klaus A, et. al.
    • Journal Title

      Proc Natl Acad Sci U S A. 104

      Pages: 18531-18536

    • Peer Reviewed
  • [Journal Article] Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene.2007

    • Author(s)
      Aoki, K, et. al.
    • Journal Title

      J. Cell Sci. 120

      Pages: 3327-3335

    • Peer Reviewed
  • [Journal Article] Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.2007

    • Author(s)
      Wrobel CN, et. al.
    • Journal Title

      Dev Biol. 309

      Pages: 285-297

    • Peer Reviewed
  • [Journal Article] Cranial neural crest cells regulate head muscle patterning and differentiation during vertebrate enbryogenesis.2007

    • Author(s)
      Rinon A, et. al.
    • Journal Title

      Development 134

      Pages: 3065-3075

    • Peer Reviewed
  • [Journal Article] Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling.2007

    • Author(s)
      Kojima, Y, et. al.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 23532-23540

    • Peer Reviewed
  • [Journal Article] Phases of canonical Wnt signaling during the development of mouse intestinal epithelium.2007

    • Author(s)
      Kim BM, et. al.
    • Journal Title

      Gastroenterology 133

      Pages: 529-538

    • Peer Reviewed
  • [Journal Article] Ciliary margin transdifferentiation from neural retina is controlled by canonical Wnt signaling.2007

    • Author(s)
      Liu H, et. al.
    • Journal Title

      Dev Biol. 308

      Pages: 54-67

    • Peer Reviewed
  • [Journal Article] Wnt/beta-catenin signaling promotes expansion of Isl-1-positive cardiac progenitor cells through regulation of FGF signaling.2007

    • Author(s)
      Cohen ED, et. al.
    • Journal Title

      J Clin Invest. 117

      Pages: 1794-1804

    • Peer Reviewed
  • [Journal Article] Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors.2007

    • Author(s)
      Kwon C, et. al.
    • Journal Title

      Proc Natl Acad Sci U S A. 104

      Pages: 10894-10899

    • Peer Reviewed
  • [Journal Article] Beta-catenin downregulation is required for adaptive cardiac remodeling.2007

    • Author(s)
      Baurand A, et. al.
    • Journal Title

      Circ Res. 100

      Pages: 1353-1362

    • Peer Reviewed
  • [Journal Article] Wnt signaling regulates pancreatic beta cell proliferation.2007

    • Author(s)
      Rulifson IC et. al.
    • Journal Title

      Proc Natl Acad Sci U S A. 104

      Pages: 6247-6252

    • Peer Reviewed
  • [Journal Article] Chromosomal instability by beta-catenin/TCF transcription in Apc or beta-catenin mutant cells.2007

    • Author(s)
      Aoki, K, et. al.
    • Journal Title

      Oncogene 26

      Pages: 3511-3520

    • Peer Reviewed
  • [Journal Article] Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes.2007

    • Author(s)
      Kawada, K, et. al.
    • Journal Title

      Oncogene 26

      Pages: 4679-4688

    • Peer Reviewed
  • [Journal Article] SMAD4-deficient intestinal tumors recruit CCR1+-myeloid cells that help invasion.2007

    • Author(s)
      Kitamura, T, et. al.
    • Journal Title

      Nat. Genet. 39

      Pages: 467-475

    • Peer Reviewed
  • [Journal Article] Wnt-beta-catenin signaling initiates taste papilla development.2007

    • Author(s)
      Liu F, et. al.
    • Journal Title

      Nat Genet. 39

      Pages: 106-112

    • Peer Reviewed
  • [Presentation] Roles of Smoothened (Smo), the major signal transducer of the hedgehog pathway, in the development of intestinal tumors.2008

    • Author(s)
      Arimura S
    • Organizer
      Proceedings of the 128th Annual Meeting of the Pharmaceutical Society of Japan (PSJ)
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      20080326-28
  • [Presentation] A Novel Mechanism of Colon Cancer Invasion: The role of CCR1 and myeloid cells2008

    • Author(s)
      Taketo, M.M.
    • Organizer
      NIH-NIDDK Workshop "Local Influences on Health and Repair of Intestinal Epithelium"
    • Place of Presentation
      Bethesda, MD, USA
    • Year and Date
      20080325-20080326
  • [Presentation] A Novel Mechanism of Colon Cancer Invasion: Role of Bone Marrow-derived Cells2008

    • Author(s)
      Taketo, M.M.
    • Organizer
      NIH-NCI-Japan Cooperative Cancer Research Program Workshop 2008
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20080319-20080321
  • [Presentation] LKB1-MARKシグナリングによるチュブリン重合抑制2007

    • Author(s)
      小島 康
    • Organizer
      日本分子生物学会・日本生化学会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
  • [Presentation] Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces martality in Apc delta716 mice2007

    • Author(s)
      藤下 晃章
    • Organizer
      日本分子生物学会・日本生化学会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
  • [Presentation] Smoothened (SMO), a transducer of the hedgehog (Hh) signaling, as a putativetherapeutic target for colon cancer2007

    • Author(s)
      有村 純暢
    • Organizer
      日本分子生物学会・日本生化学会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
  • [Presentation] Mouse Model of Gastric Cancer: Role of H. pyroli infection and Wnt signal activation2007

    • Author(s)
      Taketo, M. M.
    • Organizer
      AACR Conference "Fronteers in Cancer Prevention Research"
    • Place of Presentation
      Philadelphia, PA, USA
    • Year and Date
      20071205-08
  • [Presentation] A Novel Mechanism of Colon Cancer Invasion: Role of Bone Marrow-derived Cells2007

    • Author(s)
      Taketo, M.M.
    • Organizer
      The 38th International Symposium of Princess Takamatsu Cancer Research Fund
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20071127-20071129
  • [Presentation] A Novel Mechanism of Colon Cancer Invasion: Role of CCR1+Myeloid Cells in Smad4-deficient Colon Cancer2007

    • Author(s)
      Taketo, M. M.
    • Organizer
      AACR Meeting: Advances in Colorectal Cancer Research
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      20071114-17
  • [Presentation] Possible involvement of Notch pathway genes in colon cancer metastasis2007

    • Author(s)
      Sonoshita, M
    • Organizer
      The Notch Meeting
    • Place of Presentation
      Athens, Greece
    • Year and Date
      20070923-20070927
  • [Presentation] A Novel Mechanism of Colon Cancer Invasion: Role of Immature Myeloid Cells in a SMAD4-defficient Adenocarcinoma Mouse Model2007

    • Author(s)
      Taketo, M. M.
    • Organizer
      98th Annual Meeting of AACR
    • Place of Presentation
      Los Angeles, CA, USA
    • Year and Date
      20070413-18
  • [Presentation] Novel Mechanism of Colon Cancer Invasion: Role of Immature Myeloid Cells2007

    • Author(s)
      武藤 誠
    • Organizer
      日本癌学会・学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
  • [Presentation] SMAD4-deficient intestinal tumors secrete CCL9, and recruit CCR1^+-immature myeloid cells that help invasion2007

    • Author(s)
      北村剛規
    • Organizer
      日本癌学会・学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-04
  • [Remarks]

    • URL

      http://www4.mfour.med.kyoto-u.ac.jp/

URL: 

Published: 2010-02-04   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi