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

新規癌転移関連分子Mlzeの機能解析-消化器癌の転移における役割-

Research Project

Project/Area Number 14657131
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

篠村 恭久  大阪大学, 医学系研究科, 助教授 (90162619)

Co-Investigator(Kenkyū-buntansha) 中原 征則  大阪大学, 医学部附属病院, 医員(臨床研究)
清原 達也  大阪大学, 医学系研究科, 助教授 (50322178)
宮崎 義司  大阪大学, 医学系研究科, 助手 (30303960)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords転移 / 大腸癌 / 悪性黒色腫 / HGF / EGF / 胃癌
Research Abstract

マウス悪性黒色腫の転移能の高い細胞株から単離した新規遺伝子MLZEは悪性黒色腫ばかりでなく消化器由来の癌細胞株でも発現する。大腸腺腫、木腸癌および肝転移巣でのこの遺伝子の発現を検訂した結果、この遺伝子が大腸腺腫では発現せず大腸癌とその転移巣で発現していることを明らかにした。MLZEの機能を明らかにする目的でMLZE遺伝子をラット腸管上皮由来の細胞株IEC6細胞に遺伝子導入して細胞形態、増殖能、運動能を検討した。その結果、MLZE遺伝子導入細胞株は運動能が亢進することが明らかになった。細胞運動を亢進させる機序を明らかにするため、消化管上皮細胞の運動能を高める因子であるHGFおよびEGFによってMLZEが活性化されるかどうかをIEC6細胞において検討した。HGFおよびEGFの刺激はMLZE発現量を変化させなかった。MLZE蛋白は細胞質全体のびまん性に分布するが、GFP融合MLZE蛋白を強制発現した細胞においてHGFおよびEGFの刺激は融合蛋白の核内移行を惹起させなかった。したがって、MLZEはHGFおよびEGFによる運動能の亢進には関与しないと考えられた。MLZEはロイシンジッパー構造を持ち、ここを介して他の分子と結合する可能性がある。そこで、免疫沈降で結合相手の同定を試みた。MLZEを発現する細胞株3種の細胞抽出液を抗MLZE抗体で免疫沈降して電気泳動したが、3つの細胞株で共通するバンドは得られなかった。次にMLZEが生体内で癌細胞の転移能を亢進させる働きがあるかどうかをマウス転移モデルで検討した。MLZE発現量の少ない低転移性悪性黒色腫細胞株F10にMLZE遺伝子を導入して高発現株を作成し、これをマウス皮下に接種して肺転移能を調べたが、転移能に変化を認めなかった。

Report

(2 results)
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] K.Kinoshita, et al.: "Absence of c-kit gene mutations in gastrointestinal stromal tumours from neurofibromatosis type 1 patients."J Pathol.. 202(1). 80-85 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Kamada, et al.: "Enhanced carbon tetrachiorlde-induced liver fibrosis in mice lacking adiponectin."Gastroenterology. 125(6). 1796-1807 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Nishibayashi, et al.: "Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma."J Gastroenterol Hepatol.. 18(12). 1384-1391 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Kinoshita, et al.: "Endoscopic ultrasonography-guided fine needle aspiration biopsy in follow-up patients with gastrointestinal stromal tumours."Eur J Gastroenterol Hepatol.. 15(11). 1189-1193 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Hirota, et al.: "Gain-of-function mutations of platelet-derived growth factor receptor gene in gastrointestinal stromal tumors."Gastroenterology. 125(3). 660-667 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Ogasa, et al.: "Gastrin activates nuclear factor kappaB through a protein kinase C dependent pathway involving NFkappaB inducing kinase, inhibitor kappaB kinase, and tumour necrosis factor receptor associated factor 6 in MKN-28 cells transfected with gastrin receptor."Gut. 52(6). 813-819 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Kiyohara et al.: "A decreased number of c-kit-expressing cells in a patient with afferent loop syndrome"J.Gastroenterol.. 38(4)(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Takakura et al.: "Enhanced macrophage responsiveness to lipopolysaccharide and CD40 stimulation in a murine model of inflammatory bowel disease : IL-10-deficient mice"Inflammation Research. 51(8). 409-415 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Nakahara et al.: "Deficiency of KTT-positive cells in the colon of patients with diabetes mellitus"J.Gastroenterol.Hepatol.. 17(6). 666-670 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Murayama et al.: "Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer"Int.J.Cancer. 98(4). 505-513 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Hirota et al.: "Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KTT gene"Gastroenterology. 122(5). 1493-1499 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Ichiba et al.: "Epidermal growth factor inhibits the growth of TE8 esophageal cancer cells through the activation of STAT1"J.Gastroenterol.. 37(7). 497-503 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Toyota et al.: "Gastrin activates NF-kB through a protein kinase C-dependent pathway involving NF-kB-inducing kinase, IkB kinase and TRF6 in MKN-28 cells transected with gastrin receptor"Gut. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Nakahara et al.: "Dose-dependent and time-limited proliferation of cultured murine interstitial cells of Cajal in response to stem cell facter"Life Sciences. 70(20). 2367-2376 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Chen et al.: "Possible relationship between deficiency of interstitial cells of Cajal and colonic inertia in a patient with colon malfixation"J. Gastroenterol.. 37(6). 483-484 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Chen et al.: "Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumours"Gut. 51(6). 793-796 (2002)

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi