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2009 Fiscal Year Final Research Report

Identify the mechanism of invasion and metastasis of pancreatic cancer and development of novel treatment starategy.

Research Project

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Project/Area Number 19591594
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

ISHIKAWA Shinji  Kumamoto University, 医学部附属病院, 非常勤診療医師 (80419639)

Co-Investigator(Kenkyū-buntansha) HIROTA Masahiko  熊本大学, 医学部附属病院, 非常勤診療医師 (80284769)
TAKAMORI Hiroshi  熊本大学, 大学院・生命科学研究部, 講師 (90363514)
BABA Hideo  熊本大学, 大学院・生命科学研究部, 教授 (20240905)
Project Period (FY) 2007 – 2009
Keywords遺伝子 / 癌 / シグナル伝達 / 分子標的治療 / ORP5 / コレステロール / 膵癌
Research Abstract

The expression of oxysterol binding protein related protein (ORP) 5 is related to invasion and a poor prognosis in pancreatic cancer patients. ORP5 induced the expression of sterol response element binding protein (SREBP) 2 and activated the downstream gene of sterol response element (SRE). Chromosomal immunoprecipitation (ChIP) using SREBP2 antibody revealed that HDAC5 was one of the downstream genes of SREBP2. The effect of HMG-CoA reductase inhibitors (statins) were analyzed according to the expression level of ORP5. The invasion rate, growth was suppressed in cells that strongly expressed ORP5 in a time and dose dependent manor, but had less effect in cells weakly expressing ORP5, thus suggesting that when the potential of invasion and growth relies on the cholesterol synthesis pathway, it becomes sensitive to HMG-CoA reductase inhibitor. Furthermore, HDAC inhibitor, tricostatin A (TSA), induced the expression of phosphatase and tensin homologue (PTEN) as well when ORP5 was suppressed or the cells were treated with statin. Treatment with both statin and TSA showed a synergistic anti-tumor effect in cells that highly expressed ORP5. Therefore, in some pancreatic cancers, continuous ORP5 expression enhances the cholesterol synthesis pathway and this signal transduction regulates PTEN via HDAC5 expression. This is the first report of a detail mechanism of how the signal transduction of cholesterol synthesis is related to cancer invasion and why statins can suppress invasion and growth.

  • Research Products

    (6 results)

All 2009 2008 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] ORP5 (oxysterol-binding protein-related protein-5) is relat ed to invasion and poor prognosis in pancreatic cancer2008

    • Author(s)
      Koga Y
    • Journal Title

      Cancer Scienc e99

      Pages: 2387-94

    • Peer Reviewed
  • [Journal Article] The role of Oxyster ol binding protein related protein 5 in pancreatic cancer

    • Author(s)
      Ishikawa S
    • Journal Title

      Cancer Scie nce (in press)

    • Peer Reviewed
  • [Presentation] 局所進行膵癌に対する治療戦略2009

    • Author(s)
      森啓史
    • Organizer
      第40回日本膵臓学会大会
    • Place of Presentation
      東京都, 京王プラザホテル
    • Year and Date
      2009-07-31
  • [Presentation] Analysis of the chronic panc reatitis model mice induced the CDE die t2009

    • Author(s)
      井田智
    • Organizer
      第1回日本・モンゴル消化器癌シンポジウム
    • Place of Presentation
      ウランバートル(モンゴル), モンゴル国立がんセンター
    • Year and Date
      2009-04-29
  • [Presentation] コレステロール合成経路とORP5:膵癌浸潤とスタチンの効果のメカニズム2008

    • Author(s)
      石川晋之
    • Organizer
      第63回日本消化器外科学会
    • Place of Presentation
      札幌, ロイトン札幌・札幌プリンスホテル
    • Year and Date
      2008-07-16
  • [Presentation] 脂質代謝関連遺伝子ORP5と膵臓癌浸潤との関係2008

    • Author(s)
      石川晋之
    • Organizer
      第108回日本外科学会
    • Place of Presentation
      長崎, ベストウェスタンプレミアホテル長崎
    • Year and Date
      2008-05-15

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Published: 2011-06-18   Modified: 2016-04-21  

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