Genetic analysis of hormone-refractory prostate cancer in relation to the pathological diagnosis

• Project/Area Number: 18590331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kochi University
• Principal Investigator: FURIHATA Mutsuo Kochi University, 教育研究部医療学系, 教授 (10209158)
• Co-Investigator(Kenkyū-buntansha): 中川 英刀 東京大学, 医科学研究所, 助教 (50361621)
• Co-Investigator(Renkei-kenkyūsha): NAKAGAWA Hidewaki 理化学研究所, ゲノム医科学研究センターバイオマーカー探索開発チーム, チームリーダー (50361621)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,250,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥750,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: 前立腺癌 / ホルモン療法 / 遺伝子解析 / 病理診断 / 組織化学 / ホルモン非依存性前立腺癌 / 遺伝子発現異常 / マイクロアレイ解析

Research Abstract

ホルモン非依存性前立腺癌で腫瘍マーカーとなりうる癌関連遺伝子候補を同定することができた。これらは前立腺癌増殖の促進に関与する新規癌関連遺伝子や、既存の癌関連遺伝子でGIe器on分類に相関して発現が亢進するものも同定している。新規癌関連遺伝子産物として同定したPKIBの連遺伝子産物を抗原として抗体を作製した。作製した抗体を用いて免疫組織化学的に前立腺癌症例を検討したところ、その発現は、正常前立腺では減弱しているが、癌組織では高発現がみられ、ホルモン非依存性前立腺癌においては、特にGleasonscoreが高い症例に有意に高発現を示す結果となった。

Research Products

• [Journal Article] Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer (2009)
  • Author(s): Tamura K, Furihata M, et.al.
  • Journal Title: Cancer Sci. 100(5)(投稿中)(掲載確定) Pages: 914-919
  • NAID: 10025145832
  • Peer Reviewed
• [Journal Article] Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model : Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys (2008)
  • Author(s): Baba M, Furihata M, et.al.
  • Journal Title: J Natl Cancer Inst. 100 Pages: 140-154
  • Peer Reviewed
• [Journal Article] Over-expression of cysteine proteinase inhibitor cystatin 6 promotes pancreatic cancer growth (2008)
  • Author(s): Hosokawa M, Kashiwaya K, Eguchi H, Ohigashi H, Ishikawa O, Furihata M, et.al.
  • Journal Title: Cancer Sci. 99 Pages: 1626-1632
  • NAID: 10024009979
  • Peer Reviewed
• [Journal Article] A highly bone marrow metastatic murine breast cancer model established through in vivo selection exhibits enhanced anchorage-independent growth and cell migration mediated by ICAM-1 (2008)
  • Author(s): Takahashi M, Furihata M, et.al.
  • Journal Title: Clin Exp Metastasis 25 Pages: 517-529
  • Peer Reviewed
• [Journal Article] Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model : Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys. (2008)
  • Author(s): Baba M, Furihata M, et al.
  • Journal Title: J Natl Cancer Inst. 100 Pages: 140-154
  • Peer Reviewed
• [Journal Article] Over-expression of cysteine proteinase inhibitor cystatin 6 promotes pancreatic cancer growth. (2008)
  • Author(s): Hosokawa M, Kashiwaya K, Eguchi H, Ohigashi H, Ishikawa O, Furihata M, et al.
  • Journal Title: Cancer Sci. 99 Pages: 1626-1632
  • NAID: 10024009979
  • Peer Reviewed
• [Journal Article] A highly bone marrow metastatic murine breast cancer model established through in vivo selection exhibits enhanced anchorage-independent growth and cell migration mediated by ICAM-1. (2008)
  • Author(s): Takahashi M, Furihata M, et al.
  • Journal Title: Clin Exp Metastasis. 25 Pages: 517-529
  • Peer Reviewed
• [Journal Article] Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys (2008)
  • Author(s): BaBa M, Furihata M, et. al.
  • Journal Title: J Natl Cancer Inst 100 Pages: 140-54
  • Peer Reviewed
• [Journal Article] A highly bone marrow metastatic murine breast cancer model established through in vivo selection exhibits enhanced anchorage-independent growth and cell migration mediated by ICAM-1 (2008)
  • Author(s): Takahashi M, Furihata M, et. al.
  • Journal Title: Clin Exp Metastasis (印刷中)
  • Peer Reviewed
• [Journal Article] Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles (2007)
  • Author(s): Tamura K, Furihata M, et.al.
  • Journal Title: Cancer Res. 67 Pages: 5117-5125
  • Peer Reviewed
• [Journal Article] Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles (2007)
  • Author(s): Tamura K, Furihata M, et. al.
  • Journal Title: Cancer Res 67 Pages: 5117-5125
  • Peer Reviewed
• [Journal Article] Modification in the von Hippel-Lindau protein is involved in the progres sion of experimentally induced rat glomerulonephritis (2007)
  • Author(s): Kudo Y, et. al.
  • Journal Title: Nephron Exp Nephrol 106
  • Peer Reviewed
• [Journal Article] Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants). Increases with high Gleason score and prostate cancer progression (2006)
  • Author(s): Ashida S, Furihata M, et.al.
  • Journal Title: Clin Cancer Res. 12 Pages: 2767-2773
  • Peer Reviewed
• [Journal Article] Vascular defects and liver damage by the acute inactivation of the VHL gene during mouse embryogenesis (2006)
  • Author(s): Hong SB, Furihata M, et al.
  • Journal Title: Laboratory Investigation 86 Pages: 664-675
• [Journal Article] Expression of novel molecules,MICAL2-PV(MICAL2 prostate cancer variants ), increases with high Gleason score and prostate cancer progression. (2006)
  • Author(s): Ashida S, Furihata M, et al.
  • Journal Title: Clinical Cancer Research 12 Pages: 2767-2773
• [Journal Article] A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion (2006)
  • Author(s): Takeuchi T, Adachi Y, Sonobe H, Furihata M, et al.
  • Journal Title: Oncogene 25 Pages: 7059-7069
• [Journal Article] Posttranslational phosphorylation of mutant p53 protein in tumor development. (2006)
  • Author(s): Matsumoto M, Furihata M, et al.
  • Journal Title: Medical Molecular Morphology 39 Pages: 79-87
  • NAID: 10020338010
• [Journal Article] Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. (2006)
  • Author(s): Baba M, et al.
  • Journal Title: Proceedings of the National Academy of Science of the USA 103 Pages: 15552-15557
• [Journal Article] PCOTH, a novel gene over-expressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-I beta/SET (2005)
  • Author(s): Anazawa Y, Nakagawa H, Furihata M, et.al.
  • Journal Title: Cancer Res. 65 Pages: 4578-4586
  • Peer Reviewed
• [Presentation] ホルモン療法抵抗性前立腺がんで発現上昇を認める新規分子標的遺伝子PKA-associatedprotein(PKAP)に対する機能解析 (2008)
  • Author(s): 鄭秀蓮, 降幡睦夫, 田村賢司, 植村元秀, 柏谷琴映, Lianhua Piao, 醍醐弥太郎, 那須保友, 三木恒治, 執印太郎, 藤岡知昭, 中村祐輔, 中川英刀
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 去勢抵抗性前立腺癌に標的を絞った, ゲノム研究により前立腺癌に対する治療分子標的の同定 (2008)
  • Author(s): 中川英刀, 植村元秀, チョンスヨン, 降幡睦夫, 田村賢司, 柏谷琴映, 朴蓮花, 植田幸嗣, 那須保友, 三木恒治, 執印太郎, 藤岡知昭, 中村祐輔
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 低酸素環境におけるリガンド依存性Notch活性化の制御システム (2008)
  • Author(s): 竹内保, 降幡睦夫
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] がんの細胞異型に迫る一核異型に対する科学的アプローチー (2007)
  • Author(s): 笹野公伸, 佐々木功典, 降幡睦夫, 林慎一, 井上正樹
  • Organizer: 第46回日本臨床細胞学会秋季大会
  • Place of Presentation: 仙台
• [Presentation] ホルモン不応性前立腺癌細胞の遺伝子発言解析 (2006)
  • Author(s): 中川英刀, 田村賢司, 降幡睦夫, 鄭秀蓮, 吉岡弘樹, 中鶴修一, 三木恒治, 藤岡知昭, 執印太郎
  • Organizer: 第65回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] ホルモン不応性前立腺癌で発現上昇を認めるkinaseの同定とその機能解析 (2006)
  • Author(s): 鄭秀蓮, 中川英刀, 田村賢司, 吉岡弘樹, 中鶴修一, 降幡睦夫, 三木恒治, 藤岡知昭, 執印太郎, 中村祐輔
  • Organizer: 第65回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 前立腺癌に対する分子標的EARM(fatty acidrelated molecule)の機能解析 (2006)
  • Author(s): 田村賢司, 中川英刀, 降幡睦夫, 鄭秀蓮, 吉岡弘樹, 藍田真吾, 中鶴修一, 三木恒治, 藤岡知昭, 執印太郎, 中村祐輔
  • Organizer: 第65回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 前立腺癌悪性度を反映する新規分子マーカーの探索 (2006)
  • Author(s): 佐竹宏文, 藍田真吾, 降幡睦夫, 執印太郎
  • Organizer: 第65回日本癌学会総会
  • Place of Presentation: 横浜