The relationship between chronic injury and the origin of the liver tumor analyzed using mouse model

• Project/Area Number: 22590717
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: ASAOKA Yoshinari 東京大学, 医学部附属病院, 助教 (90431858)
• Co-Investigator(Kenkyū-buntansha): SASAKI Takashi 東京大学, 医学部附属病院, 助教 (10569106) ; 伊地知 秀明 東京大学, 医学部附属病院, 助教 (70463841) ; 池上 恒雄 東京大学, 医科学研究所, 准教授 (80396712)
• Co-Investigator(Renkei-kenkyūsha): IKENOUE Tsuneo 東京大学, 医科学研究所, 准教授 (80396712)
• Research Collaborator: IJICHI Hideaki 東京大学, 医学部附属病院, 助教 (70463841)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胆管癌 / マウスモデル / 肝癌 / 細胞内シグナル伝達 / 肝臓学 / 肝内胆管癌

Research Abstract

We generated hepatic cancer mouse model by inducing expression of activated Kras and ablation of Pten under albumin-promoter. The mice died from multipe liver tumor in 7 to 8 weeks. Using genomic analysis of SNP array, we found that Hippo pathway, a novel intracellular signaling, was involved in hepatocarcinogenesis. Aberration of SAV1, a component of the pathway, was shown to induce the activation of YAP/TAZ and following expression of CTGF in a liver cancer cell line.

Research Products

• [Journal Article] Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation (2012)
  • Author(s): Kudo Y, Aburatani H, et al.
  • Journal Title: Cancer Science Volume: 103 Issue: 4 Pages: 670-676
  • DOI: 10.1111/j.1349-7006.2012.02213.x
  • Peer Reviewed
• [Journal Article] Phosphorylation of Gli by cAMP-dependent protein kinase (2012)
  • Author(s): Asaoka Y.
  • Journal Title: Vitam Horm Volume: 88 Pages: 293-307
  • DOI: 10.1016/b978-0-12-394622-5.00013-4
• [Journal Article] IGF-II Producing Hepatocellular Carcinoma Treated with Sorafenib: Metabolic Complications and a Foresight to Molecular Targeting Therapy to the IGF Signal. (2012)
  • Author(s): Okushin K, Asaoka Y, Fukuda I,Fujiwara N, Minami T, Sato M, Mikami S,Uchino K, Enooku K, Kondo Y, Tateishi R, Goto T, Shiina S, Yoshida H, Koike K.
  • Journal Title: Case Rep Gastroenterol Volume: 6(3) Issue: 3 Pages: 784-9
  • DOI: 10.1159/000346462
  • Peer Reviewed
• [Journal Article] Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine. (2012)
  • Author(s): Sasaki T, Isayama H, Nakai Y, Mizuno S, Yamamoto K, YagiokaH, Yashima Y, Kawakubo K, Kogure H, Togawa O, Matsubara S, Ito Y, Sasahira N, Hirano K, Tsujino T, Toda N, Tada M, Omata M, Koike K.
  • Journal Title: Invest New Drugs Volume: 0(2) Issue: 2 Pages: 708-13
  • DOI: 10.1007/s10637-010-9553-9
  • Peer Reviewed
• [Journal Article] Reduced expression of RAS protein activator like-1 in gastric cancer (2011)
  • Author(s): Seto M, Ohta M, Ikenoue T, Sugimoto T, Asaoka Y, Tada M, Mohri D, Kudo Y, Ijichi H, Tateishi K, Otsuka M, Hirata Y, Maeda S, Koike K, Omata M.
  • Journal Title: Int J Cancer Volume: 128(6) Issue: 6 Pages: 1293-302
  • DOI: 10.1002/ijc.25459
  • Peer Reviewed
• [Journal Article] Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis. (2011)
  • Author(s): Kondo Y, Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Masuzaki R, Asaoka Y, Fujie H, Goto T, Omata M, Yoshida H, Koike K.
  • Journal Title: Liver Int Volume: 31(2) Issue: 2 Pages: 197-205
  • DOI: 10.1111/j.1478-3231.2010.02415.x
  • Peer Reviewed
• [Journal Article] Serum level of adiponectin and the risk of liver cancer development in chronic hepatitis C patients. (2011)
  • Author(s): Arano T, Nakagawa H, Tateishi R, Ikeda H, Uchino K, Enooku K, Goto E, Masuzaki R, Asaoka Y, Kondo Y, Goto T, Shiina S, Omata M, Yoshida H, Koike K.
  • Journal Title: Int J Cancer Volume: 129(9) Issue: 9 Pages: 2226-35
  • DOI: 10.1002/ijc.25861
  • Peer Reviewed
• [Journal Article] New targeted therapies for gastric cancer (2011)
  • Author(s): Asaoka Y, Ikenoue T, Koike K.
  • Journal Title: Expert Opin Investig Drugs Volume: 20(5) Issue: 5 Pages: 595-604
  • DOI: 10.1517/13543784.2011.566863
  • Peer Reviewed
• [Journal Article] Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy (2011)
  • Author(s): Sasaki T, Isayama H, Nakai Y, Togawa O, Kogure H, Ito Y, Yamamoto K, Mizuno S, Yagioka H,Yashima Y, Kawakubo K, Arizumi T, Matsubara S, Sasahira N, Hirano K, Tsujino T, Toda N, Tada M, Omata M, Koike K.
  • Journal Title: Cancer Chemother Pharmacol Volume: 67(4) Issue: 4 Pages: 847-53
  • DOI: 10.1007/s00280-010-1360-7
  • Peer Reviewed
• [Journal Article] Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer. (2011)
  • Author(s): Sasaki T, Isayama H, Nakai Y, Mizuno S, Yamamoto K, Yagioka H, Yashima Y, Kawakubo K, Kogure H, Togawa O, Matsubara S, Sasahira N, Hirano K, Tsujino T, Tada M, Omata M, Koike K.
  • Journal Title: Invest New Drugs Volume: 29(6) Issue: 6 Pages: 1488-93
  • DOI: 10.1007/s10637-010-9485-4
  • Peer Reviewed
• [Journal Article] Prognostic significance of genetic alterations detected by high-density single nucleotide polymorphism array in gastric cancer (2010)
  • Author(s): Tada M, Kanai F, Tanaka Y, Sanada M, Nannya Y, Tateishi K, Ohta M, Asaoka Y, Seto M, Imazeki F, Yoshida H, Ogawa S, Yokosuka O, Omata M
  • Journal Title: Cancer Sci Volume: 101(5) Issue: 5 Pages: 1261-9
  • DOI: 10.1111/j.1349-7006.2010.01500.x
  • NAID: 10026592643
  • Peer Reviewed
• [Journal Article] Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion. (2010)
  • Author(s): Asaoka Y, Tada M, Ikenoue T, Seto M, Imai M, Miyabayashi K, Yamamoto K, Yamamoto S, Kudo Y, Mohri D, Isomura Y, Ijichi H, Tateishi K, Kanai F, Ogawa S, Omata M, Koike K.
  • Journal Title: Biochem Biophys Res Commun Volume: 394(4) Issue: 4 Pages: 1042-6
  • DOI: 10.1016/j.bbrc.2010.03.120
  • Peer Reviewed
• [Journal Article] A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer (2010)
  • Author(s): Isomura Y, Yamaji Y, OhtaM, Seto M, Asaoka Y, Tanaka Y, Sasaki T, Nakai Y, Sasahira N, Isayama H, Tada M, Yoshida H, Kawabe T, Omata M, Koike K.J
  • Journal Title: Gastroenterol Volume: 45(10) Issue: 10 Pages: 1045-52
  • DOI: 10.1007/s00535-010-0246-0
  • NAID: 10027699389
  • Peer Reviewed
• [Journal Article] Multicenter, phase II study of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. (2010)
  • Author(s): Sasaki T, Isayama H, Nakai Y, Ito Y, Kogure H, Togawa O, Toda N, Yasuda I, Hasebe O, Maetani I,Sasahira N, Hirano K, Tsujino T, Tada M, Omata M.
  • Journal Title: Cancer Chemother Pharmacol Volume: 65(6) Issue: 6 Pages: 1101-7
  • DOI: 10.1007/s00280-009-1115-5
  • Peer Reviewed
• [Presentation] Hippoシグナル異常を伴う肝細胞癌における受容体型チロシンキナーゼに関する検討 (2011)
  • Author(s): 浅岡良成
  • Organizer: JDDW2011
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-21
• [Presentation] 肝細胞癌におけるHippoシグナルの異常に関する検討 (2011)
  • Author(s): 浅岡良成
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-03
• [Presentation] Recurrent SAV1 Mutations InHepatocellular Carcinoma (2011)
  • Author(s): Asaoka Y.
  • Organizer: APASL2011
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2011-02-20
• [Presentation] SNPアレイを用いた胃癌細胞株における受容体型チロシンキナーゼ遺伝子異常に関する検討. (2010)
  • Author(s): 浅岡良成
  • Organizer: JDDW2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-13