Molecular mechanism of hormone therapy resistance in cancers

• Project/Area Number: 21590450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• Principal Investigator: KUWATA Takeshi 独立行政法人国立がん研究センター, 臨床開発センター, 医長 (00327321)
• Co-Investigator(Kenkyū-buntansha): OCHIAI Atsushi 独立行政法人国立がん研究センター, 臨床開発センター, 部長 (60183034)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 腫瘍 / 前立腺 / アンドロゲン / 核内受容体 / 病理学 / 前立腺癌 / ホルモン依存性癌

Research Abstract

Molecular mechanism of hormone therapy resistance, especially in prostate cancer, was investigated. Interleukin(IL)-1beta showed tumor inhibitory effect in several prostate cancer cell lines including LNCap, while a previous report suggested possible involvement of IL-1beta in the resistance. Constitutive expression of these enzymes support tumor cell growth in castrated nude mice. Thus we concluded that these results suggested expression of androgenic enzymes may be involved in acquired resistant against hormone therapy in cancer.

Research Products

• [Journal Article] Targeting of bone-derived insulin-like growth factor-II by a humanizing antibody suppresses the growth of prostate cancer cells in a human bone environment (2010)
  • Author(s): Kimura T, Kuwata T, Ashimine S, Yamazaki M, Yamauchi C, Nagai K, Ikehara A, Feng Y, Dimitrov DS, Saito S, Ochiai A
  • Journal Title: Clinical Cancer Research Volume: 16巻 Issue: 1 Pages: 121-129
  • DOI: 10.1158/1078-0432.ccr-09-0982
  • Peer Reviewed
• [Journal Article] Pin1 acts as a modulator of cell proliferation through alteration in NF-κB but not β-catenin/TCF4 signalling in a subset of endometrial carcinoma cells. (2010)
  • Author(s): Saegusa S, Kuwata T, et al
  • Journal Title: J Pathol Volume: 222 Pages: 410-420
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of pro-apoptotic Par-4 by NF-kappaB/p65 and its function incontrolling cell kinetics during early events in endometrial tumourigenesis. (2010)
  • Author(s): Saegusa T, Kuwata T, et al
  • Journal Title: J Pathol Volume: 221 Pages: 26-36
  • Peer Reviewed
• [Journal Article] Targeting of bone-derived insulin-like growth factor-II by a humanizing antibody suppresses the growth of prostate cancer cells in a human bone environment (2010)
  • Author(s): Kimura T
  • Journal Title: Clinical Cancer Research 16 Pages: 121-9
  • Peer Reviewed
• [Presentation] Aldo-keto reductase(AKR) 1C3 expression is frequently observed in human prostate cancer cases after androgen-therapy and promotes prostate cancer cell growth in castrated mice model AACR-EORTC-NCI Molecular Targets and Cancer (2011)
  • Author(s): Kuwata T and Ochiai A
  • Organizer: Therapeutics Conference
  • Place of Presentation: 米国
  • Year and Date: 2011-11-14
• [Presentation] Aldo-keto reductase (AKR) 1C3 expression is frequently observed in human prostate cancer cases after androgen-therapy and promotes prostate cancer cell growth in castrated mice model (2011)
  • Author(s): Takeshi Kuwata
  • Organizer: AACR-EORTC-NCI Molecular Targets and Cancer Therapeutics Conference
  • Place of Presentation: SanFran Cisco, USA
  • Year and Date: 2011-11-14
• [Presentation] 前立腺癌の抗アンドロゲン療法抵抗性獲得におけるアンドロゲン合成酵素発現の関与 (2011)
  • Author(s): 桑田健、落合淳志
  • Organizer: 日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-30
• [Presentation] 前立腺癌の抗アンドロゲン療法抵抗性獲得におけるアンドロゲン合成酵素発現の役割 (2011)
  • Author(s): 桑田健
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-30
• [Presentation] 前立腺癌の抗アンドロゲン療法抵抗性におけるステロイド合成酵素発現の関与 (2010)
  • Author(s): 桑田健、落合淳志
  • Organizer: 日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-28