Analysis of the expression and function of SIRT1 in endometrial carcinoma

• Project/Area Number: 24791696
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: ASAKA Ryoichi 信州大学, 医学部附属病院, 医員 (00623688)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Sirtuin1 / 子宮内膜癌 / シスプラチン耐性 / SIRT1阻害剤 / EX527 / 長寿遺伝子 / 脱アセチル化 / p53 / 増殖能

Research Abstract

The immunohistochemical expression of Sirtuin1 (SIRT1) was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (p<0.05), and its overexpression was associated with a shorter survival (p<0.05). The WST-1 assay revealed that SIRT1 accelerated the proliferation and cisplatin resistance of endometrial carcinoma cell lines (HHUA, HEC151 and HEC1B). Whereas the selective SIRT1 inhibitor (EX527) suppressed the proliferation and cisplatin resistance of those cell lines regardless of the
p53 mutation. The effects of SIRT1 on tumor growth were examined in vivo using mice xenografts of HHUA and HEC1B cells. SIRT1 overexpression significantly increased tumor growth, however, EX527 significantly suppressed tumor growth in nude mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy.

Research Products

• [Journal Article] Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia (2013)
  • Author(s): Kobara H, Miyamoto T, Suzuki A, Asaka R, Yamada Y, Ishikawa K, Kikuchi N, Ohira S, Shiozawa T
  • Journal Title: Placenta Volume: 34 Pages: 1036-43
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of core 2 β1, 6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma : a novel potential prognostic factor (2013)
  • Author(s): Miyamoto T, Suzuki A, Asaka R, Ishikawa K, Yamada Y, Kobara H, Nakayama J, Shiozawa T
  • Journal Title: Histopathology Volume: 62 Pages: 986-93
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma: a novel potential prognostic factor. (2013)
  • Author(s): Miyamoto T
  • Journal Title: Histopathology Volume: Feb 9 [Epub ahead of print] Issue: 7 Pages: 986-93
  • DOI: 10.1111/his.12107
  • Peer Reviewed
• [Journal Article] Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia. (2013)
  • Author(s): Kobara H, Miyamoto T, Suzuki A, Asaka R, Yamada Y, Ishikawa K, Kikuchi N, Ohira S, Shiozawa T.
  • Journal Title: Placenta Volume: 34(11) Issue: 11 Pages: 1036-43
  • DOI: 10.1016/j.placenta.2013.08.004
• [Presentation] Sirtuin1, a longevity gene, is over-expressed and enhances proliferation and survival of endometrial carcinoma cells via deacetylation of p53 (2013)
  • Author(s): Asaka R, Miyamoto T, Ishikawa K, Yamada Y, Kobara H, Suzuki A, Taniguchi S, Shiozawa T
  • Organizer: American Assosiation for Cancer Research Annual Meeting 2013
  • Place of Presentation: ワシントン D.C
  • Year and Date: 2013-04-07
• [Presentation] Sirtuin1(SIRT1) inhibitor suppressrs tumor growth of endometrial carcinoma cell in nude mice (2013)
  • Author(s): Asaka R, Miyamoto T, Ando H, YamadaY, David Hamisi Mvunta, Ishikawa K, Kobara H, Shiozawa T
  • Organizer: 第3回アジア婦人科腫瘍学会・第55回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 京都
• [Presentation] SIRT1は子宮内膜癌細胞において PI3K およびMAPK 経路を介して, 増殖能亢進とシスプラチン耐性獲得に関与する (2013)
  • Author(s): 浅香亮一, 宮本 強, 安藤大史, 石川香織, 山田 靖, 小原久典, 塩沢丹里
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 長寿遺伝子sirtuin1の子宮内膜癌細胞における増殖・抗癌剤耐性に関する作用の検討 (2013)
  • Author(s): 浅香亮一, 宮本 強, 石川香織, 山田 靖, 小原久典, 塩沢丹里
  • Organizer: 第12回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 奈良
• [Presentation] 長寿遺伝子のSirtuin1の子宮内膜癌における発現と機能の検討 (2013)
  • Author(s): 浅香亮一, 宮本 強, 安藤大史, 石川香織, 山田 靖, 塩沢丹里
  • Organizer: 第18回生殖医学フォーラム
  • Place of Presentation: 松本
• [Presentation] Sirtuin1は子宮内膜癌のシスプラチン耐性に関与する (2013)
  • Author(s): 浅香亮一, 宮本 強, 石川香織, 山田 靖, 小原久典, 鈴木昭久, 塩沢丹里
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
• [Presentation] SIRT1は子宮内膜癌細胞においてPI3KおよびMAPK経路を介して、増殖能亢進とシスプラチン耐性獲得に関与する (2013)
  • Author(s): 浅香亮一、宮本 強、安藤大史、石川香織、山田 靖、小原久典、塩沢丹里
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Sirtuin1(SIRT1) inhibitor suppressrs tumor growth of endometrial carcinoma cell in nude mice. (2013)
  • Author(s): Asaka R,Miyamoto T,Ando H,Yamada Y,David Hamisi Mvunta,Ishikawa K,Kobara H,Shiozawa T.
  • Organizer: 第3回アジア婦人科腫瘍学会・第55回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 京都
• [Presentation] Sirtuin1(SIRT1), a longevity gene, is over-expressed in endometrial carcinoma (2012)
  • Author(s): Asaka R, Miymamoto T, Suzuki A, Ishikawa K, Yamada Y, Kobara H, Shiozawa T
  • Organizer: 14th International Gynecologic Cancer Society(IGCS)
  • Place of Presentation: バンクーバー
• [Presentation] 正常内膜および子宮内膜癌におけるSirtuin1(SIRT1)の発現と機能の検討 (2012)
  • Author(s): 浅香亮一, 宮本 強, 石川香織, 山田 靖, 小原久典, 鈴木昭久, 塩沢丹里
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 正常子宮内膜および子宮内膜癌における sirtuin1 発現の検討 (2012)
  • Author(s): 浅香亮一, 宮本 強, 鈴木昭久, 鹿島大靖, 塩沢丹里
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] 正常子宮内膜および子宮内膜癌におけるsirtuin1発現の検討 (2012)
  • Author(s): 浅香 亮一
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] Sirtuin1(SIRT1),a longevity gene,is over-expressed in endometrial carcinoma (2012)
  • Author(s): Asaka R
  • Organizer: 14th International Gynecologic Cancer Society(IGCS)
  • Place of Presentation: Vancouver
• [Presentation] Sirtuin1, a longevity gene, is over-expressed and enhances proliferation and survival of endometrial carcinoma cells via deacetylation of p53
  • Author(s): Asaka R,Miyamoto T, Ishikawa K,Yamada Y, Kobara H,Suzuki A, Taniguchi S,Shiozawa T.
  • Organizer: American Assosiation for Cancer Research Annual Meeting 2013
  • Place of Presentation: Washington, DC