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Pre-clinical applications using PTEN-knockout prostate cancer mouse model

Research Project

Project/Area Number 22591781
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKinki University

Principal Investigator

DE VELASCO Marco  近畿大学, 医学部, 助教 (20449838)

Co-Investigator(Kenkyū-buntansha) UEMURA Hirotsugu  近畿大学, 医学部, 教授 (90213397)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords前立腺癌 / PTEN / ノックアウトマウス / 動物モデル / バイオマーカー / マウスモデル / Cre-LoxPシステム / 去勢抵抗性がん / マーカー
Research Abstract

To better understand the disease process of prostate cancer, we have developed a prostate-specific conditional knockout mouse model that targets the PTEN tumor suppressor gene. Our model is based on PSA-Cre recombinase driven inactivation of Pten to alter PI3K/Akt/mTOR signaling specific to the prostate, resulting in a stage-specific development and progression of cancer that mimics humans recapitulating various stages of disease progression ranging from precancerous PIN lesions to castration resistant prostate cancer. We performed several experiments that demonstrate the versatility and usefulness of this model for validation of preclinical targeted intervention, biomarker discovery (leptin, lumican and HOXA10) and characterizing lifestyle behavior effects on cancer progression.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (42 results)

All 2013 2012 2011 2010 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (28 results)

  • [Journal Article] Slug increases sensitivity to tubulin-binding agents via the downregulation of βIII and βIVa-tubulin in lung cancer cells.2013

    • Author(s)
      Tamura D, Arao T, Nagai T, Kaneda H, Aomatsu K, Fujita Y, Matsumoto K, Velasco MA, et al.
    • Journal Title

      Cancer Med

      Volume: 2(2) Pages: 144-54

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preclinical remodeling of human prostate cancer through the PTEN/Akt pathway2012

    • Author(s)
      De Velasco MA and Uemura H
    • Journal Title

      Adv Urol

      Volume: 2012 Pages: 419348-419348

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors.2012

    • Author(s)
      Fujita Y, Islam R, De Velasco MA, et al.
    • Journal Title

      Invest New Drugs

      Volume: 30(5) Pages: 1878-86

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway.2012

    • Author(s)
      De Velasco MA, Uemura H.
    • Journal Title

      Adv Urol.

      Volume: - Pages: 1-12

    • DOI

      10.1155/2012/419348

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors.2012

    • Author(s)
      Fujita Y, de Velasco MA, Nishio K. et. Al.
    • Journal Title

      Invest New Drugs.

      Volume: 30 Issue: 5 Pages: 1878-1886

    • DOI

      10.1007/s10637-011-9749-7

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] eclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway2012

    • Author(s)
      M D Velasco
    • Journal Title

      Adv Urol.2012

      Volume: volume2012 Pages: 1-12

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer2011

    • Author(s)
      Kaneda H, Arao T, De Velasco MA, et al.
    • Journal Title

      Br J Cancer

      Volume: 105(8) Pages: 1210-7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor activity of BIBF 1120, a triple angiokinase inhibitor, and use of VEGFR2+pTyr+ peripheral blood leukocytes as a pharmacodynamic biomarker in vivo.2011

    • Author(s)
      Kudo K, Arao T, De Velasco MA et al.
    • Journal Title

      Clin Cancer Res

      Volume: 17(6) Pages: 1373-81

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system2011

    • Author(s)
      Zennami K, Yoshikawa K, Kondo E,, De Velasco MA, Tanaka M, Uemura H, et al.
    • Journal Title

      Oncol Rep.

      Volume: 26 Pages: 327-333

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival.2011

    • Author(s)
      Shimada K, Anai S, DeVelasco, et al.
    • Journal Title

      MA BMC Urol.

      Volume: 11:8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system2011

    • Author(s)
      K Zennami
    • Journal Title

      Oncol Rep

      Volume: 26 Pages: 327-333

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor Activity of BIBF 1120, a Triple Angiokinase Inhibitor, and Use of VEGFR2+pTyr+ Peripheral Blood Leukocytes as a Pharmacodynamic Biomarker In Vivo2011

    • Author(s)
      K Kudo
    • Journal Title

      Clin Cancer Res

      Volume: 17 Pages: 1373-1381

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma.2010

    • Author(s)
      Shimada K, Nakamura M, De Velasco MA et al.
    • Journal Title

      Cancer Sci

      Volume: 101(1) Pages: 155-60

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth2010

    • Author(s)
      Kaneda H, Arao T, De Velasco MA, et al
    • Journal Title

      Cancer Res

      Volume: 70(5) Pages: 2053-63

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Leptin contributes to prostate cancer progression.2013

    • Author(s)
      Marco A De Velasco, Yutaka Yamamoto, Yuji Hatanaka, Yurie Kura, Naomi Ando, Emiko Fukushima, Masahiro Noazawa, Nobutaka Shimizu, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Noshio, Hirotsugu Uemura.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-04-09
    • Related Report
      2012 Final Research Report
  • [Presentation] Interleukin-6 (IL-6) as a therapeutic target in prostate cancer.2013

    • Author(s)
      Yurie Kura, Marco A De Velasco, Yasuyuki Kobayashi, Naomi Ando, Emiko Fukushima, Yutaka Yamamoto, Yuji Hatanaka, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-04-08
    • Related Report
      2012 Final Research Report
  • [Presentation] Therapeutic potential of JAK/STAT signal inhibition in prostate cancer by the JAK inhibitor AZD14802013

    • Author(s)
      Marco A. De Velasco, Hirotsugu Uemura, et al
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-04-07
    • Related Report
      2012 Final Research Report
  • [Presentation] A ole for lumican as a biomarker of disease progression in human prostate adenocarcinoma2013

    • Author(s)
      Marco A De Velasco, Hirotsugu Uemura, et al
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-04-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Preclinical responses of the MEK inhibitor AZD6244 in a genetically modified mouse model of prostate cancer2013

    • Author(s)
      Hirotsugu Uemura, Marco A De Velasco, et al
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-04-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Autophagy is required for prostate cancer progression2013

    • Author(s)
      Marco A De Velasco, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-04-07
    • Related Report
      2012 Final Research Report
  • [Presentation] 前立腺癌マウスモデルに対する分子標的治療薬の抗腫瘍効果の検討2012

    • Author(s)
      山本豊、デベラスコ マルコ、倉由吏恵、畑中祐二、吉村一宏、清水信貴、野澤昌弘、吉川和宏、西尾和人、植村天受
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒト前立腺癌の進展におけるHOXA10 の発現異常について2012

    • Author(s)
      畑中祐二、デベラスコ マルコ、植村天受、他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 前立腺特異的PTENノックアウトマウスにおけるSTAT3 の転写活性に関する検討2012

    • Author(s)
      小林泰之、デベラスコ マルコ、植村天受、他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Diet-induced leptin contributes to prostate cancer progression2012

    • Author(s)
      Marco A De Velasco, Hirotsugu Uemura, et al.
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒト前立腺がんにおけるルミカンの発現について2012

    • Author(s)
      吉村一宏、デベラスコ マルコ、植村天受、他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Role of Stat3 transcriptional activation in a preclinical mouse model of prostate cancer and potential as a therapeutic target2012

    • Author(s)
      De Velasco MA, Uemura H, et al.
    • Organizer
      Cancer Res
    • Year and Date
      2012-04-15
    • Related Report
      2012 Final Research Report
  • [Presentation] Enhanced anti-tumor effects using a combinatorial targeted treatment strategy in a preclinical model of prostate cancer2012

    • Author(s)
      De Velasco MA, Uemura H, et al
    • Organizer
      Cancer Res
    • Year and Date
      2012-04-15
    • Related Report
      2012 Final Research Report
  • [Presentation] Evaluation of lumican expression profiles in prostate cancer2012

    • Author(s)
      K.Yoshimura
    • Organizer
      AACR
    • Place of Presentation
      シカゴ
    • Year and Date
      2012-04-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Role of Stat3 trnscriptional activation in a preclinical mouse model of prostate cancer and potential as a terapeutic target2012

    • Author(s)
      M DeVelasco
    • Organizer
      AACR
    • Place of Presentation
      シカゴ
    • Year and Date
      2012-04-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Use of a novel synthetic biomaterial to induce mild whole body hyperthermia for the treatment of cancer in a preclinical model2012

    • Author(s)
      M.Kodama
    • Organizer
      AACR
    • Place of Presentation
      シカゴ
    • Year and Date
      2012-04-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] HOXA10 expression profiles in prostate cancer2012

    • Author(s)
      Y.Hatanaka
    • Organizer
      AACR
    • Place of Presentation
      シカゴ
    • Year and Date
      2012-04-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Enhanced anti-tumor effects using a combinatorial targeted treatment strategy in a preclinical model of prostate cancer2012

    • Author(s)
      Y.Yamamoto
    • Organizer
      AACR
    • Place of Presentation
      シカゴ
    • Year and Date
      2012-04-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] A preclinical model to evaluate the risk of increased dietary fat consumption and prostate cancer progression2012

    • Author(s)
      Y.Kobayashi
    • Organizer
      AACR
    • Place of Presentation
      シカゴ
    • Year and Date
      2012-04-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ptenノックアウト前立腺癌モデルにおけるsorafenibの治療効果2011

    • Author(s)
      山本豊
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] The prostate-specific PTEN conditional knockout mouse as a model for human prostate cancer2010

    • Author(s)
      De Velasaco M., Uemura H., et al.
    • Organizer
      69th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      大阪市
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Anti-tumor effects of everolimus and chlormadinone acetate against prostate cancer in a pre-clinical mouse model2010

    • Author(s)
      De Velasaco M., Uemura H., et al.
    • Organizer
      69th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      大阪市
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pre-clinical chemopreventive efficacy of chlormadinone acetate against prostate cancer2010

    • Author(s)
      Koike H., De Velasco M., Uemura H., et al
    • Organizer
      69th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      大阪市
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] A role for iumican as a biomarker of disease progression in human prostate adenocarcinoma

    • Author(s)
      De Verasco M., Hatanaka Y., Uemura H. et.al.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Preclinical responses of the MEK inhibitor AZD6244 in an genetically modified mouse model of prostate cancer

    • Author(s)
      Uemura H., Kura Y., De Velasco M. et.al.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Interleukin-6(IL-6) as a therapeutic target in prostate cancer

    • Author(s)
      Kura Y., De Velasco M., Uemura H. et.al.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Leptin contributes to prostate cancer

    • Author(s)
      De Velasco M., Yamamot Y., Uemura H. et.al.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Autophagy is required for prostate cancer progression

    • Author(s)
      De Velasco M., Y. Kura, Uemura H. et.al.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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