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

• Project/Area Number: 22591781
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kinki 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: ¥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.

Research Products

• [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
  • Peer Reviewed
• [Journal Article] Preclinical remodeling of human prostate cancer through the PTEN/Akt pathway (2012)
  • Author(s): De Velasco MA and Uemura H
  • Journal Title: Adv Urol Volume: 2012 Pages: 419348-419348
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] eclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway (2012)
  • Author(s): M D Velasco
  • Journal Title: Adv Urol.2012 Volume: volume2012 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer (2011)
  • Author(s): Kaneda H, Arao T, De Velasco MA, et al.
  • Journal Title: Br J Cancer Volume: 105(8) Pages: 1210-7
  • 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
  • Peer Reviewed
• [Journal Article] A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system (2011)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system (2011)
  • Author(s): K Zennami
  • Journal Title: Oncol Rep Volume: 26 Pages: 327-333
  • 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): K Kudo
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 1373-1381
  • 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
  • Peer Reviewed
• [Journal Article] FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth (2010)
  • Author(s): Kaneda H, Arao T, De Velasco MA, et al
  • Journal Title: Cancer Res Volume: 70(5) Pages: 2053-63
  • 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
• [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
• [Presentation] Therapeutic potential of JAK/STAT signal inhibition in prostate cancer by the JAK inhibitor AZD1480 (2013)
  • 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
• [Presentation] A ole for lumican as a biomarker of disease progression in human prostate adenocarcinoma (2013)
  • 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
• [Presentation] Preclinical responses of the MEK inhibitor AZD6244 in a genetically modified mouse model of prostate cancer (2013)
  • 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
• [Presentation] Autophagy is required for prostate cancer progression (2013)
  • 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
• [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
• [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
• [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
• [Presentation] Diet-induced leptin contributes to prostate cancer progression (2012)
  • 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
• [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
• [Presentation] Role of Stat3 transcriptional activation in a preclinical mouse model of prostate cancer and potential as a therapeutic target (2012)
  • Author(s): De Velasco MA, Uemura H, et al.
  • Organizer: Cancer Res
  • Year and Date: 2012-04-15
• [Presentation] Enhanced anti-tumor effects using a combinatorial targeted treatment strategy in a preclinical model of prostate cancer (2012)
  • Author(s): De Velasco MA, Uemura H, et al
  • Organizer: Cancer Res
  • Year and Date: 2012-04-15
• [Presentation] Evaluation of lumican expression profiles in prostate cancer (2012)
  • Author(s): K.Yoshimura
  • Organizer: AACR
  • Place of Presentation: シカゴ
  • Year and Date: 2012-04-04
• [Presentation] Role of Stat3 trnscriptional activation in a preclinical mouse model of prostate cancer and potential as a terapeutic target (2012)
  • Author(s): M DeVelasco
  • Organizer: AACR
  • Place of Presentation: シカゴ
  • Year and Date: 2012-04-03
• [Presentation] Use of a novel synthetic biomaterial to induce mild whole body hyperthermia for the treatment of cancer in a preclinical model (2012)
  • Author(s): M.Kodama
  • Organizer: AACR
  • Place of Presentation: シカゴ
  • Year and Date: 2012-04-03
• [Presentation] HOXA10 expression profiles in prostate cancer (2012)
  • Author(s): Y.Hatanaka
  • Organizer: AACR
  • Place of Presentation: シカゴ
  • Year and Date: 2012-04-03
• [Presentation] Enhanced anti-tumor effects using a combinatorial targeted treatment strategy in a preclinical model of prostate cancer (2012)
  • Author(s): Y.Yamamoto
  • Organizer: AACR
  • Place of Presentation: シカゴ
  • Year and Date: 2012-04-02
• [Presentation] A preclinical model to evaluate the risk of increased dietary fat consumption and prostate cancer progression (2012)
  • Author(s): Y.Kobayashi
  • Organizer: AACR
  • Place of Presentation: シカゴ
  • Year and Date: 2012-04-01
• [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
• [Presentation] The prostate-specific PTEN conditional knockout mouse as a model for human prostate cancer (2010)
  • 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
• [Presentation] Anti-tumor effects of everolimus and chlormadinone acetate against prostate cancer in a pre-clinical mouse model (2010)
  • 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
• [Presentation] Pre-clinical chemopreventive efficacy of chlormadinone acetate against prostate cancer (2010)
  • 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
• [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
• [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
• [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
• [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
• [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