Analysis of ovarian tumourigenesis due to activators for histone deacetylases(HDACs) that are highly overexpressed in cancers

• Project/Area Number: 21592129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: HIGASHITSUJI Hisako 京都大学, 医学研究科, 助教 (20402852)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ガンキリン / HSCO / ヒストン脱アセチル化酵素 / 卵巣癌 / 活性化因子 / HDAC1 / SIRT1 / がん抑制遺伝子 / ヒストン / 脱アセチル化酵素

Research Abstract

Protooncogene Gankyrin is overexpressed in ovarian cancer. Gankyrin accelerates to degrade pRb protein. Gankyrin inhibits the interaction of p16INK4a with cdk4. Gankyrin enhances to degrade p53 protein by MDM2. Gankyrin suppresses the activity of NFkappaB, partly due to recruitment of SIRT1 histone deacetylase to NFkappaB protein. HSCO gene is overexpressed in ovarian cancer. HSCO inhibits the activity of p53 due to recruitment of HDAC1 histone deacetylase to p53 protein. Gankyrin and HSCO activate the activity of HDACs. These enhanced activities of HDACs accelerate to grow cancer cells more aggressively. The activities of invasion and metastasis are enhanced due to these activated HDACs. Nicotinamide suppresses SIRT1 activity. TSA(Trichostatin A) inhibits HDAC1 activity. These HDAC inhibitors suppress the growth, invasion, and metastasis of cancer cells.

Research Products

• [Journal Article] Adriamycin enhances proteasome-mediated generation of the proapoptotic processed form of MAGE-A4 in hepatoma cells (2011)
  • Author(s): Sakurai T, Kudo M, Itoh K, Ryu U, Higashitsuji H, Fujita J.
  • Journal Title: Oncology Volume: 81 Issue: Suppl. 1 Pages: 30-5
  • DOI: 10.1159/000334307
• [Journal Article] Adriamycin enhances proteasome-mediated generation of the proapoptotic processed form of MAGEA-4 in hepatoma cells (2011)
  • Author(s): Sakurai T., et al
  • Journal Title: Oncology Volume: 81 Pages: 30-35
  • Peer Reviewed
• [Journal Article] MDM2 is a novel E3 ligase for HIV-1 Vif (2009)
  • Author(s): Izumi T, Takaori-Kondo A, Shirakawa K, Higashitsuji H, Itoh K, Io K, Matsui M, Iwai K, Kondoh H, Sato T, Tomonaga M, Ikeda S, Akari H, Koyanagi Y, Fujita J, Uchiyama T.
  • Journal Title: Retrovirology Volume: 6 Issue: 1 Pages: 1-10
  • DOI: 10.1186/1742-4690-6-1
  • Peer Reviewed
• [Journal Article] MDM2 is a novel E3 ligase for HIV-1 Vif. (2009)
  • Author(s): Izumi T
  • Journal Title: Retrovirology 6 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Association of gankyrin protein expression with early clinical stages and IGFBP-5 expression in human hepatocellular carcinoma (2008)
  • Author(s): Umemura A, Itoh Y, Itoh K, Yamaguchi K, Nakajima T, Higashitsuji H, Onoue H, Fukumoto M, Okanoue T, Fujita J.
  • Journal Title: Hepatology Volume: 47(2) Issue: 2 Pages: 493-502
  • DOI: 10.1002/hep.22027
  • Peer Reviewed
• [Journal Article] Gankyrin oncoprotein overexpression as a critical factor for tumor growth in human esophageal squamous cell carcinoma and its clinical significance (2008)
  • Author(s): Ortiz CM, Ito T, Tanaka E, Tsunoda S, Nagayama S, Sakai Y, Higashitsuji H, Fujita J, Shimada Y.
  • Journal Title: Int J Cancer Volume: 122 Issue: 2 Pages: 325-332
  • DOI: 10.1002/ijc.23106
  • Peer Reviewed
• [Presentation] CIRP(cold-inducible RNA binding protein)は癌細胞の浸潤能、転移能を亢進する (2011)
  • Author(s): 東辻久子
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: リーガロイヤルホテル大阪、大阪市
  • Year and Date: 2011-08-30
• [Presentation] CIRP (cold-inducible RNA binding protein)は癌細胞の浸潤能、転移能を亢進する (2011)
  • Author(s): 東辻久子
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪市、リーガロイヤルホテル大阪
  • Year and Date: 2011-08-30
• [Presentation] がん遺伝子CIRP(cold-inducible RNA binding protein)は癌細胞の浸潤能と転移能を亢進させる (2010)
  • Author(s): 東辻久子
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2010-10-14
• [Presentation] がん遺伝子CIRP(cold-inducible RNA binding protein)は癌細胞の浸潤能と転移能を亢進させる (2010)
  • Author(s): 東辻久子
  • Organizer: JDDW2010第52回日本消化器病学会大会
  • Place of Presentation: 横浜市パシフィコ横浜
  • Year and Date: 2010-10-14
• [Presentation] 卵巣癌で過剰発現するがん遺伝子ガンキリンはNFkappaB(RelA)と結合しその転写活性化能を抑制する (2009)
  • Author(s): 東辻久子
  • Organizer: 第61回日本産科婦人科学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市
  • Year and Date: 2009-04-05
• [Presentation] 卵巣癌で過剰発現する癌遣伝子産物ガンキリンはNFkappaB(RelA)と結合しその転写活性化能を抑制する。 (2009)
  • Author(s): 東辻久子
  • Organizer: 第61回日本産科婦人科学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市
  • Year and Date: 2009-04-05