New aspect of lipid signaling by analyzing PTEN-regulatory molecules

2010 Fiscal Year Self-evaluation Report

• Project/Area Number: 20249019
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: SUZUKI Akira Kyushu University, 生体防御医学研究所, 教授 (10311565)
• Project Period (FY): 2008 – 2011
• Keywords: PTEN / PI3キナーゼ / がん抑制遺伝子

Research Abstract

細胞のがん化には多くのシグナル伝達分子が関与している.そのうちの一つであるホスホイノシチド-3-キナーゼ(PI3K)シグナルは、多くの細胞外シグナルの下流分子として機能することが知られている。そのシグナルを負に制御するPTENは、がん抑制遺伝子として単離され、ヒトの悪性腫瘍の半数にも異常が認められている。このように、PTENはがん化に極めて重要な機能を有しているにもかかわらず、その制御機構はほとんど明らかになっていない。
本研究課題では、(1)PTENの各種臓器における機能解析、(2)PTEN蛋白質を安定化するがん抑制遺伝子候補分子PICT1の機能解析、(3)PTENを活性化する新規がん抑制遺伝子候補分子PBP1の解析の合計3つのアプローチによって、PTEN/PI3K経路研究の新展開をめざす。

Research Products

• [Journal Article] Regulation of the MDM2-p53 pathway and tumor growth by PICT1/GLTSCR2 via nucleolar RPL11. (2011)
  • Author(s): Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wang J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Zhu Y, Prives C, Nakano T, Mak TW, Sasaki T, Maehama T, Mori M, Suzuki A.
  • Journal Title: NATURE MEDICINE in press
• [Journal Article] Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways. (2011)
  • Author(s): Ikegami D, Akiyama H, Suzuki A, Nakamura T, Nakano T, Yoshikawa H, Tsumaki N.
  • Journal Title: DEVELOPMENT 138(8) Pages: 1507-1519
• [Journal Article] HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion. (2010)
  • Author(s): Patzak IM, Konigsberger S, Suzuki A, Mak TW, Kiefer F.
  • Journal Title: EUROPEAN LOURNAL OF IMMUNOLOGY 40(11) Pages: 3220-3225
• [Journal Article] Deletion of Pten in pancreatic beta-cells protects against deficient beta cell mass and function in mouse models of type 2 diabetes (2010)
  • Author(s): Wang L, Liu Y, Yan Lu S, Nguyen KT, Schroer SA, Suzuki A, Mak TW, Gaisano H, Woo M
  • Journal Title: DIABETES 59(12) Pages: 3117-3126
• [Journal Article] The PtdIns(3,4)P2-phosphatase INPP4A is a suppressor of excitotoxic neuronal death. (2010)
  • Author(s): Sasaki J, Kofuji S, Itoh R, Momiyama T, Takayama K, Murakami H, Chida S, Tsuya Y, Takasuga S, Eguchi S, Asanuma K, Horie Y, Miura K, Davis M, Mitchell C, Yamazaki M, Hirai H, Takenawa T, Suzuki A, Sasaki T
  • Journal Title: NATURE 465(7297) Pages: 497-501
• [Journal Article] Nod-like receptor signaling enhances dendritic cell-mediated cross-priming in vivo. (2010)
  • Author(s): Asano J, Tada H, Onai N, Sato T, Horie Y, Fujimoto Y, Fukase K, Suzuki A, Mak TW, Ohteki T
  • Journal Title: JOURNAL OF IMMUNOLOGY 184(2) Pages: 736-745
• [Journal Article] Mammalian phosphoinositide kinases and phosphatases (2009)
  • Author(s): Sasaki T, Takasuga S, Sasaki J, Kofuji S, Eguchi S, Yamazaki M, Suzuki A
  • Journal Title: PROGRESS IN LIPID RESEARCH 48(6) Pages: 478-487
• [Journal Article] Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice. (2009)
  • Author(s): Ishii H, Horie Y, Ohshima S, Anezaki Y, Kinoshita N, Dohmen T, Kataoka E, Sato W, Goto T, Sasaki J, Sasaki T, Watanabe S, Suzuki A, Ohnishi H.
  • Journal Title: JOURNAL OF HEPATOLOGY 50(3) Pages: 562-571
• [Journal Article] PTEN deletion and concomitant c-Myc activation does not lead to tumor formation in pancreatic beta cells. (2009)
  • Author(s): Radziszewska A, Choi D, Nguyen KT, Schroer SA, Tajmir P, Wang L, Suzuki A, Mak TW, Evan GI, Woo M
  • Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY 284(5) Pages: 2917-2922
• [Journal Article] Phosphatase and tensin homolog (PTEN) regulates hepatic lipogenesis, microsomal triglyceride transfer protein, and the secretion of apolipoprotein B-containing lipoproteins. (2008)
  • Author(s): Qui W, Federico L, Naples M, Avramoglu RK, Meshkani R, Zhang J, Tsai J, Hussain M, Iqbai J, Kontos CD, Horie Y, Suzuki A, Adeli K
  • Journal Title: HEPATOLOGY 48(6) Pages: 1799-1809
• [Journal Article] The role of PTEN in development, physiology and tumorigenesis in mouse models : a tissue-by-tissue survey (2008)
  • Author(s): Knobbe CB, Lapin V, Suzuki A, Mak TW
  • Journal Title: ONCOGENE 27(41) Pages: 5398-5415
• [Journal Article] Pten deficiency in melanocytes results in resistance to hair graying and susceptiblity to carcinogen-induced melanomagenesis (2008)
  • Author(s): Inoue-Narita T, Hamada K, Sasaki T, Hatakeyama S, Fujita S, Kawahara K, Sasaki M, Kishimoto H, Eguchi S, Kojima I, Beermann F, Kimura T, Osawa M, Itami S, Mak TW, Nakano T, Manabe M, Suzuki A
  • Journal Title: CANCER RESAERCH 68(14) Pages: 5760-5768
• [Journal Article] Partial deletion of PTEN in the hypothalamus leads to growth defects that cannot be rescued by exogenous growth hormone (2008)
  • Author(s): Choi D, Nguyen KT, Wang L, Schroer S, Suzuki A, Mak TW, Woo M
  • Journal Title: ENDOCRINOLOGY 149(9) Pages: 4382-4386
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages (2008)
  • Author(s): Kuroda S, Nishio M, Sasaki T, Horie Y, Kawahara K, Sasaki M, Natsui M, Matozaki T, Tezuka H, Ohteki T, Forster I, Mak TW, Nakano T, Suzuki A
  • Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY 38(5) Pages: 1331-1340
• [Journal Article] Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice (2008)
  • Author(s): Xue L, Nolla H, Suzuki A, Mak TW, Winoto A
  • Journal Title: PROCEEDING OF NATIONAL ACADEMY OF SCIENCE USA 105(6) Pages: 2022-2027
• [Journal Article] Portrait of PTEN : Messages from Mutant Mice (2008)
  • Author(s): Suzuki A, Nakano T, Mak TW, Sasaki T
  • Journal Title: CANCER SCIENCE 9(2) Pages: 209-213
• [Presentation] Idetification of a novel gene PICT1/GLTSCR2 which regulates MDM2-p53 pathway and tumor growth (2010)
  • Author(s): 河原康一.河原康一、佐々木雅人、西尾美希、古後龍之介、三森功士、濱田浩一、伊東文祥、佐々木雄彦、前濱朝彦、森正樹、鈴木聡
  • Organizer: 第69回日本癌学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas (2008)
  • Author(s): Yanagi S, Nakazato M, Suzuki A.
  • Organizer: 第13回日韓がん国際ワークショップ
  • Place of Presentation: 大田,Korea
  • Year and Date: 2008-12-20
• [Book] 造血器腫瘍アトラス 改訂第4版(造血幹細胞を制御する遺伝子-PTEN遺伝子) (2009)
  • Author(s): 矢島伸之、鈴木聡
  • Total Pages: 54-59
• [Patent(Industrial Property Rights)] Suppression of onset and development of cancer by suppressing GLTSCR2/PICT1 (2010)
  • Inventor(s): 鈴木聡, 他5名
  • Industrial Property Rights Holder: 鈴木聡, 他5名
  • Industrial Property Number: 米国プロビジョナル出願,61/368, 880
  • Filing Date: 2010-07-29
  • Overseas