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Chronic pancreatitis triggers factors promoting pancreatic cancer development in genetically engineered mouse model

Research Project

Project/Area Number 22791291
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

OHMURAYA Masaki  熊本大学, 大学院・先導機構, 特任助教 (60398229)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膵臓外科学 / 遺伝子改変マウス / 慢性膵炎モデルマウス / SPINK1/Spink3 / 慢性膵炎 / X染色体不活性化 / SPINK1/Sink3 / 膵癌 / 膵癌モデルマウス
Research Abstract

The mutations of serine protease inhibitor Kazal type 1(SPINK1) are associated with chronic pancreatitis(CP). We previously showed that deletion of Spink3, the mouse homologue of SPINK1, causes pancreatitis-like changes in the mouse. The aim of this study was to rescue the Spink3-/-phenotype by generating Spink3-/-mice with knockin SPINK1.(Methods) We placed CAG-SPINK1 gene(SP1) into X chromosome. X-inactivation is a process whereby one of the two copies of the X chromosome present in female mammals is inactivated. By utilizing X-inactivation, we were able to create mice in which SPINK1 level was partially, but not completely, reduced. The SP1 knockin mice were crossed to Spink3+/-mice.(Results) The pancreas of Spink3-/-XSP1/+mice at birth contained both normal and degenerated acinar cells, with accumulation of autophagic vacuoles. The Spink3-/-XSP1/+mice developed pathologic features of human CP, including loss of acinar cells and fibrosis with activated stellate cells. Older mice displayed acinar-ductal metaplasia and prominent expression of proto-oncogenes Egfr, Her2, and Ras.(Conclusions) The results indicate that CP trigger factors promoting pancreatic cancer development.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (25 results)

All 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 10 results) Presentation (9 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Role of Intrapancreatic SPINK1/Spink3 Expression in the Development of Pancreatitis2012

    • Author(s)
      Ohmuraya M, Sugano A, Hirota M, Takaoka Y, Yamamura K.
    • Journal Title

      Front Physiol

      Volume: 3 Pages: 126-126

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Roles of serine protease inhibitor Kazal type 1(SPINK1) in pancreatic diseases2011

    • Author(s)
      Ohmuraya M, Yamamura K
    • Journal Title

      Exp Anim

      Volume: 60(5) Pages: 433-44

    • NAID

      130001271633

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Roles of Serine Protease Inhibitor Kazal Type 1 (SPINK1) in Pancreatic Diseases2011

    • Author(s)
      Ohmuraya M., et al
    • Journal Title

      Experimental Animals

      Volume: 60 Issue: 5 Pages: 433-444

    • DOI

      10.1538/expanim.60.433

    • NAID

      130001271633

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] オートファジーの測定・解析方法2011

    • Author(s)
      大村谷昌樹
    • Journal Title

      Surgery Frontier

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Chronic pancreatitis in mice by treatment with choline-deficient ethionine-supplemented diet2010

    • Author(s)
      Ida S, Ohmuraya M, Hirota M, Ozaki N, Hiramatsu S, Uehara H, Takamori H, Araki K, Baba H, Yamamura K
    • Journal Title

      Exp Anim

      Volume: 59(4) Pages: 421-9

    • NAID

      130000298602

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship of strain-dependent susceptibility to experimentally induced acute pancreatitis with regulation of Prss1 and Spink3 expression2010

    • Author(s)
      Wang J, Ohmuraya M, Suyama K, Hirota M, Ozaki N, Baba H, Nakagata N, Araki K, Yamamura K
    • Journal Title

      Lab Invest

      Volume: 90(5) Pages: 654-64

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transgenic expression of pancreatic secretory trypsin inhibitor-1 rescues SPINK3-deficient mice and restores a normal pancreatic phenotype2010

    • Author(s)
      Romac JM, Ohmuraya M, Bittner C, Majeed MF, Vigna SR, Que J, Fee BE, Wartmann T, Yamamura K, Liddle RA
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 298(4)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship of strain-dependent susceptibility to experimentally induced acute pancreatitis with regulation of Prss1 and Spink3 expression.2010

    • Author(s)
      Wang J
    • Journal Title

      Lab Invest

      Volume: 90 Pages: 654-64

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic pancreatitis in mice by treatment with choline-deficient ethionine-supplemented diet.2010

    • Author(s)
      Ida S
    • Journal Title

      Experimental animals

      Volume: 59 Pages: 421-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transgenic expression of pancreatic secretory trypsin inhibitor-1 rescues SPINK3-deficient mice and restores a normal pancreatic phenotype.2010

    • Author(s)
      Romac JM
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 298

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膵炎におけるオートファジーの意義2010

    • Author(s)
      大村谷昌樹
    • Journal Title

      胆と膵

      Volume: 31 Pages: 559-64

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 急性膵炎発症とオートファジー2010

    • Author(s)
      大村谷昌樹
    • Journal Title

      Medical Science Digest

      Volume: 36 Pages: 22-5

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Role of intrapancreatic SPINK1/Spink3 expression in the development of pancreatitis

    • Author(s)
      Ohmuraya M
    • Journal Title

      Frontiers in Gastrointestinal Sciences

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] X染色体不活性化による遺伝子改変慢性膵炎モデルマウスの樹立2011

    • Author(s)
      大村谷昌樹
    • Organizer
      第42回日本膵臓学会
    • Place of Presentation
      弘前市、ホテルニューキャッスル
    • Year and Date
      2011-07-30
    • Related Report
      2011 Final Research Report
  • [Presentation] X染色体不活性化による遺伝子改変慢性膵炎モデルマウスの樹立2011

    • Author(s)
      大村谷昌樹
    • Organizer
      第42回日本膵臓学会
    • Place of Presentation
      ホテルニューキャッスル(弘前市)
    • Year and Date
      2011-07-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Serine protease inhibitor Kazal type 1 activates the mammalian target of rapamycin2010

    • Author(s)
      大村谷昌樹
    • Organizer
      第69会日本癌学会
    • Place of Presentation
      大阪市、大阪国際会議場
    • Year and Date
      2010-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Serine protease inhibitor Kazal type 1 activates the mammalian target of rapamycin.2010

    • Author(s)
      Masaki Ohmuraya
    • Organizer
      第69回 日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場/大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Serine protease inhibitor Kazal type 3の発現解析2010

    • Author(s)
      大村谷昌樹
    • Organizer
      第24回モロシヌス研究会
    • Place of Presentation
      ホテルグリーンピア南阿蘇/熊本
    • Year and Date
      2010-09-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pancreatic acinar cell death pathways2010

    • Author(s)
      Masaki Ohmuraya
    • Organizer
      第14回国際膵臓学会、第41回日本膵臓学会大会
    • Place of Presentation
      福岡市、福岡国際会議場
    • Year and Date
      2010-07-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Pancreatic Acinar cell death pathways in acute pancreatitis.2010

    • Author(s)
      Masaki Ohmuraya
    • Organizer
      Joint meeting of the international association of pancreatology and the Japan pancreas society 2010
    • Place of Presentation
      福岡国際会議場/Fukuoka
    • Year and Date
      2010-07-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] A Mouse Line Expressing Spink3-Driven Cre Recombinase in acute pancreatitis2010

    • Author(s)
      Masaki Ohmuraya
    • Organizer
      THE 42st MEETING OF EPC in Stockholm
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2010-06-18
    • Related Report
      2011 Final Research Report
  • [Presentation] A mouse line expressing Spink3-driven cre recombinasae.2010

    • Author(s)
      Masaki Ohmuraya
    • Organizer
      42^<nd> Meeting of European Pancreatic Club
    • Place of Presentation
      Clarion Hotel Sign(Sweden)
    • Year and Date
      2010-06-17
    • Related Report
      2010 Annual Research Report
  • [Book] 疾患モデルマウス表現型解析指南(3章疾患モデルマウス:臓器・疾患別解析・実験法膵臓2011

    • Author(s)
      山村研一、若菜茂晴編集
    • Total Pages
      477
    • Publisher
      中山書店
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://sendou.kuma-u.jp/research/ohmuratani.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://sendou.kuma-u.jp/research/ohmuratani.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-11-30   Modified: 2016-04-21  

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