Proteomic analysis of the regulation of proteins by NO-induced posttranslational modification and anti-cancer therapy

• Project/Area Number: 20591633
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: SUGITA Hiroki Kumamoto University, 医学部附属病院, 非常勤診療医師 (30398218)
• Co-Investigator(Kenkyū-buntansha): TAKAMORI Hiroshi 熊本大学, 大学院・生命科学研究部, 講師 (90363514) ; HIROTA Masahiko 熊本大学, 医学部附属病院, 非常勤診療医師 (80284769) ; KAMOHARA Hidenobu 熊本大学, 医学部附属病院, 講師 (90398222)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: insulin / IGFシグナル / 癌 / 一酸化窒素(NO) / ユビキチン化 / IGF-I / IRS-1 / Akt/PKB / 膵癌 / EGF / MEK / Akt / PKB / 一酸化窒素

Research Abstract

NO inhibits the phosphorylation of IGF-IR, EGFR, Akt and IRS-1 protein expression, but upregulates Ras/Erk pathway in cancer cells (pancreatic and colon cancer cells). C terminus is responsible site for NO-induced ubiqutination and degradation of IRS-1 protein. NO inhibits the proliferation and invasion of pancreatic, colon and breast cancer cells. Combination of NO-donor and MEK-inhibitor enhances anti-cancer activity in these cancer cells.

Research Products

• [Journal Article] Nitric oxide inhibits proliferation and invasion activity of pancreatic cancer cells through degradation of insulin receptor substrate-1 protein (2010)
  • Author(s): Sugita H, Masao K aneki, Masahiko Hirota, Satoshi Furuhashi, Hiroshi Takamori, Hideo Baba-
  • Journal Title: Mol Cancer Res. 8 Pages: 1152-1163
  • Peer Reviewed
• [Journal Article] Pancreatoduodenectomy using a no-touch isolation technique. (2010)
  • Author(s): Hirota M, Kanemitsu K, Takamori H, Chikamoto A, Tanaka H, Sugita H, Sand J, Nordback I, Baba H.
  • Journal Title: Am J Surg. 199(5)
  • Peer Reviewed
• [Journal Article] Serum HGF and TGF-betal levels after right portal vein embolization (2010)
  • Author(s): Hayashi H, Beppu T, Sugita H, Masuda T, Okabe H, Takamori H, Baba H.
  • Journal Title: Hepatol Res. 40(3) Pages: 311-317
  • Peer Reviewed
• [Journal Article] Nitric oxide inhibits proliferation and invasion activity of pancreatic cancer cells through degradation of insulin receptor substrate-1 protein (2010)
  • Author(s): Sugita H, Kneki M, Furuhashi S, Takamori H, Horino K, Baba H
  • Journal Title: Mol Cancer Res. Volume: 8 Pages: 1152-1163
  • Peer Reviewed
• [Journal Article] Serum HGF and TGF-beta1 levels after right portal vein embolization (2010)
  • Author(s): Hayashi H, Beppu T, Sugita H, Masuda T, Okabe H, Takamori H, Baba H
  • Journal Title: Hepatol Res. Volume: 40 Pages: 311-317
  • Peer Reviewed
• [Journal Article] Pancreatoduodenectomy using a no-touch isolation technique. (2010)
  • Author(s): Hirota M, Kanemitsu K, Takamori H, Chikamoto A, Tanaka H, Sugita H, Sand J, Nordback I, Baba H.
  • Journal Title: Am J Surg. Volume: 199 Pages: 65-68
  • Peer Reviewed
• [Journal Article] Increase in the serum bile acid level predicts the effective hypertrophy of the nonembolized hepatic lobe after right portal vein embolization. (2009)
  • Author(s): Hayashi H, Beppu T,Sugita H, Horino K, Komori H, Masuda T, Okabe H, Takamori H, Baba H.
  • Journal Title: World J Surg 33(9) Pages: 1933-1940
  • Peer Reviewed
• [Journal Article] MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. (2009)
  • Author(s): Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, Yoshida N, Toyama E, Hayashi N, Watanabe M, Baba H.
  • Journal Title: Clin Cancer Res. 15(6) Pages: 1915-1922
  • Peer Reviewed
• [Journal Article] Increase in the serum bile acid level predicts the effective hypertrophy of the nonembolized hepatic lobe after right portal vein embolization (2009)
  • Author(s): Hayashi H
  • Journal Title: World J Surg 33 9 Pages: 1933-1940
  • Peer Reviewed
• [Journal Article] Pancreatoduodenectomy using a no-touch isolation technique. (2008)
  • Author(s): Hirota M, Kanemitsu K, Takamori H, Chikamoto A, Tanaka H, Sugita H, Sand J, Nordback I, Baba H.
  • Journal Title: Am J Surg.
  • Peer Reviewed
• [Presentation] The role of nitric oxide in growth factor signaling of cancer cells. (2011)
  • Author(s): 杉田裕樹, 古橋聡, 馬場秀夫
  • Organizer: World DNA and Genome Day
  • Place of Presentation: Dalian EXPO Center, Dalian, China
  • Year and Date: 2011-04-28
• [Presentation] 膵癌細胞におけるNO(一酸化窒素)によるPI3-K/Akt pathway制御機構の検討 (2010)
  • Author(s): 杉田裕樹、古橋聡、高森啓史、馬場秀夫
  • Organizer: 日本外科学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
  • Year and Date: 2010-04-09
• [Presentation] 膵癌細胞株におけるNO donorおよびMEK inhibitorの併用による抗腫瘍効果の検討 (2010)
  • Author(s): 古橋聡、杉田裕樹、阿部真也、中原修、井田智、尾崎宣之、田中洋、堀野敬、高森啓史、別府透、馬場秀夫
  • Organizer: 日本外科学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
  • Year and Date: 2010-04-09
• [Presentation] 膵癌細胞におけるNO(一酸化窒素)によるPI3-K/Akt pathway制御機構の検討 (2010)
  • Author(s): 杉田裕樹、古橋聡、高森啓史、馬場秀夫
  • Organizer: 日本外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-09
• [Presentation] 膵癌細胞株におけるNO donorおよびMEK inhibitorの併用による抗腫瘍効果の検討 (2010)
  • Author(s): 古橋聡、杉田裕樹、阿部真也、中原修、 井田智、 尾崎宣之、田中洋、堀野敬、高森啓史、別府透、馬場秀夫
  • Organizer: 日本外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-09
• [Presentation] 膵癌に対する集学的治療施行例における早期死亡率の検討 (2009)
  • Author(s): 高森啓史
  • Organizer: 第21日本肝胆膵外科学会・学術集会
  • Place of Presentation: 愛知 ウェスティンナゴヤキャッスル
  • Year and Date: 2009-06-10
• [Presentation] 膵癌細胞において発現するiNOSによるinsulin/IGFシグナルの制御 (2008)
  • Author(s): 杉田裕樹、廣田昌彦、市原敦史、馬場秀夫
  • Organizer: 日本外科学会総会
  • Place of Presentation: 長崎ブリックホール、長崎
  • Year and Date: 2008-05-15
• [Remarks] ホームページ等
  • URL: http://www2.kuh.kumamoto-u.ac.jp/shoukakigeka/html/kenkyu/kenkyu02.html
• [Remarks] 熊本大学消化器外科ホームページ