Functional analysis of a tumor suppressor gene PTEN in vivo

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013014
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University (2008-2009); Akita University (2005-2007)
• Principal Investigator: SUZUKI Akira Kyushu University, 生体防御医学研究所, 教授 (10311565)
• Project Period (FY): 2005 – 2009
• Keywords: 遺伝子改変動物 / 分子腫瘍学 / 疾患モデル動物2

Research Abstract

We analyzed the functions of PTEN/PI3kinase pathway by generating PTEN tissue specific knock-out mice. Results show that PTEN deficiency causes various cancers and non-cancerous diseases. Therefore, these mutant mice have become attractive and powerful tools to analyze these diseases and to develop new therapeutic methods.

Research Products

• [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 (in press)
  • Peer Reviewed
• [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 Vol.184(2) Pages: 736-745
  • Peer Reviewed
• [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 Vol.284(5) Pages: 2917-2922
  • Peer Reviewed
• [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 Vol.48(6) Pages: 1799-1809
  • Peer Reviewed
• [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 Vol.27(41) Pages: 5398-5415
  • Peer Reviewed
• [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 Vol.68(14) Pages: 5760-8
  • Peer Reviewed
• [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 Vol.149(9) Pages: 4382-6
  • Peer Reviewed
• [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 Vol.38(5) Pages: 1331-40
  • Peer Reviewed
• [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 Vol.105(6) Pages: 2022-2027
  • Peer Reviewed
• [Journal Article] Portrait of PTEN:Messages from Mutant Mice (2008)
  • Author(s): Suzuki A, Nakano T, Mak TW, Sasaki T
  • Journal Title: CANCER SCIENCE Vol.9(2) Pages: 209-13
  • Peer Reviewed
• [Journal Article] Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation (2007)
  • Author(s): Plum L, Rother E, Munzberg H, Wunderlich FT, Morgan DA, Hampel B, Shanabrough M, Janoschek R, Konner AC, Alber J, Suzuki A, Krone W, Horvath TL, Rahmouni K, Bruning JC
  • Journal Title: CELL METABOLISM Vol.6(6) Pages: 431-445
  • Peer Reviewed
• [Journal Article] Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas (2007)
  • Author(s): Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M, Yajima N, Hamada K, Horie Y, Kubo H, Mak TW, Nakano T, Nakazato M, Suzuki A
  • Journal Title: JOURNAL OF CLINICAL INVESTIGATION Vol.117(10) Pages: 2929-40
  • Peer Reviewed
• [Journal Article] Non-invasive visualization of the lipid product of class I PI3K in transgenic mouse models (2007)
  • Author(s): Sasaki T, Sasaki J, Watanabe K, Suzuki A
  • Journal Title: BIOCHEMICAL SOCIETY TRANSACTION Vol.35(Pt2) Pages: 215-8
  • Peer Reviewed
• [Journal Article] The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells (2007)
  • Author(s): Kishimoto H, Ohteki T, Yajima N, Kawahara K, Natsui M, Kawarasaki S, Hamada K, Horie Y, Kubo Y, Arase S, Taniguchi M, Vanhaesebroeck B, Mak TW, Nakano N, Koyasu S, Sasaki T, Suzuki A
  • Journal Title: BLOOD Vol.109(8) Pages: 3316-24
  • Peer Reviewed
• [Journal Article] Role of Pten/PI3K pathway in endothelial cells (2007)
  • Author(s): Suzuki A, Hamada K, Sasaki T, Mak TW, Nakano T
  • Journal Title: Biochemical Society Transaction Vol.35(Pt2) Pages: 172-6
  • Peer Reviewed
• [Journal Article] Control of Cell Polarity and motility byPI(3, 4, 5)P3 phosphatase (2007)
  • Author(s): Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, Iizuka R, Bella T, Yamazaki M, Watanabe H, Kuroda S, Itoh R, Forster I, Mak TW, Kanaho Y, Yonehara H, Penninger JM, Suzuki A(equal last author), Sasaki T.
  • Journal Title: SHIP NATURE CELL BIOLOGY Vol.9(1) Pages: 36-44
  • Peer Reviewed
• [Journal Article] Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients (2006)
  • Author(s): Tsuruta H, Kishimoto H, Sasaki T, Horie Y, Natsui M, Shibata Y, Hamada K, Yajima N, Kawahara K, Sasaki M, Tsuchiya N, Enomoto K, Mak TW, Nakano T, Habuchi T, Suzuki A
  • Journal Title: CANCER RESEARCH Vol.66(17) Pages: 8389-96
  • Peer Reviewed
• [Journal Article] Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN (2006)
  • Author(s): Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, Wang F, Guo A, Walczysko P, Gu Y, Sasaki T, Suzuki A, Forrester JV, Bourne HR, Devreotes PN, McCaig CD, Penninger JM
  • Journal Title: NATURE Vol.442(7101) Pages: 457-60
  • Peer Reviewed
• [Journal Article] Enhanced PIP3 Signaling in POMC Neurons Causes Neuronal Silencing via KATP Channel Activation and Leads to Diet-sensitive Obesity (2006)
  • Author(s): Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Munzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Bruning JC
  • Journal Title: JOURNAL OF CLINICAL INVESTIGATION Vol.116(7) Pages: 1886-901
  • Peer Reviewed
• [Journal Article] Essential role of Pten in body size determination and pancreatic beta cell homeostasis in vivo (2006)
  • Author(s): Nguyen KT, Tajmir P, Lin CH, Liadis N, Zhu XD, Eweida M, Tolasa-Karaman G, Cai F, Wang R, Kitamura T, Belsham DD, Wheeler MB, Suzuki A, Mak TW, Woo M
  • Journal Title: MOLECULAR AND CELLULAR BIOLOGY Vol.26(12) Pages: 4511-8
  • Peer Reviewed
• [Journal Article] Hepatocic gene expression in hepatocyte-specific Pten deficient mice showing steatohepatitis without ethanol challenge (2006)
  • Author(s): Sato W, Horie Y, Kataoka E, Ohshima S, Dohmen T, Iizuka M, Sasaki J, Sasaki T, Hamada K, Kishimoto H, Suzuki A, Watanabe S
  • Journal Title: HEPATOLOGY RESEARCH Vol.34(4) Pages: 256-65
  • Peer Reviewed
• [Journal Article] Neonatal estrogen exposure suppress PTEN-related endometrial carcinogenesis in recombinant mice (2006)
  • Author(s): Begum M, Tashiro H, Katabuchi H, Suzuki A, Kurman RJ, Okamura H
  • Journal Title: LABORATORY INVESTIGATION Vol.86(3) Pages: 286-296
  • Peer Reviewed
• [Journal Article] The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis (2005)
  • Author(s): Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J, Yajima N, Hasegawa G, Miyazaki J, Suda T, Itoh H, Nakao K, Mak TW, Nakano T, Suzuki A
  • Journal Title: GENES AND DEVELOPMENT Vol.19(17) Pages: 2054-2065
  • Peer Reviewed
• [Journal Article] Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I alpha (2005)
  • Author(s): Sasaki J, Sasaki T, Yamazaki M, Matsuoka K, Taya C, Shitara H, Takasuga S, Nishio M, Mizuno K, Wada T, Miyazaki H, Watanabe H, Iizuka R, Kubo S, Murata S, Chiba T, Maehama T, Hamada K, Kishimoto H, Frohman MA, Tanaka K, Penninger JM, Yonekawa H, Suzuki A, Kanaho Y
  • Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE Vol.201(6) Pages: 859-870
  • Peer Reviewed
• [Journal Article] Muscle-specific Pten deletion protects against insulin resistance and diabetes (2005)
  • Author(s): Wijesekara N, Konrad D, Edeida M, Jefferies C, Liadis N, Giacca A, Crockower M, Suzuki A, Mak TW, Kahn CR, Klip A, Woo M
  • Journal Title: MOLECULAR AND CELLULAR BIOLOGY Vol.25(3) Pages: 1135-1145
  • Peer Reviewed
• [Journal Article] Hepatocyte-specific Pten deficient mice as a novel model for nonalcoholic steatohepatitis and hepatocellolar carcinoma (2005)
  • Author(s): Watanabe S, Horie Y, Suzuki a
  • Journal Title: HEPATPLOGY RESEACH Vol.33 Pages: 161-166
  • Peer Reviewed
• [Presentation] PTEN結合分子PICT1の機能解析 (2009)
  • Author(s): 西尾美希、河原康一、佐々木雅人、前濱朝彦、佐々木雄彦、鈴木聡
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] PTEN結合分子PICT1の機能解析 (2009)
  • Author(s): 河原康一、佐々木雅人、西尾美希、濱田浩一、前濱朝彦、佐々木雄彦、鈴木聡
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-03
• [Presentation] Functions of PTEN in various tissues Pohang Conference on Cellular (2008)
  • Author(s): Akira Suzuki
  • Organizer: Signaling -Phospholipid-mediated signaling ligands and diseases-
  • Place of Presentation: POSTECH Biotech Center
  • Year and Date: 20080200
• [Presentation] Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas (2008)
  • Author(s): Shigehisa Yanagi, Masamitsu Nakazato, Akira Suzuki
  • Organizer: 第13回日韓がんワークショップ
  • Place of Presentation: 韓国・大田
  • Year and Date: 2008-12-13
• [Presentation] pi3k/aktシグナルによる多能性幹細胞システムの制御 (2008)
  • Author(s): 木村透、中村肇伸、山野範子、山本敏之、鈴木聡、仲野徹
  • Organizer: bmb学術集会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-12
• [Presentation] PTEN欠損による肺腺がんとメラノーマのマウスモデルの樹立ーPTENと組織幹細胞 (2008)
  • Author(s): 鈴木聡、柳重久、中里雅光、井上多恵、真鍋求、濱田浩一、河原康一、佐々木雅人、西尾美希、仲野徹、佐々木雄彦
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] PTENによる組織幹細胞制御 (2007)
  • Author(s): 鈴木聡井上多恵、柳重久、河原浩一、佐々木雅人、西尾美希、夏井美幸、真鍋求、中里雅光、仲野徹、佐々木雄彦
  • Organizer: BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 20071200
• [Presentation] PTEN/PI3K経路によるValpha14iNKT細胞の制御 (2007)
  • Author(s): 鈴木聡、岸本恕征、樗木俊聡、矢島伸之、河原康一、夏井美幸、谷口克、仲野徹、小安重夫、佐々木雄彦
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 20071000
• [Presentation] 気管支肺胞上皮におけるPTENの機能解析 (2007)
  • Author(s): 柳重久、中里雅光、鈴木聡
  • Organizer: 第47回日本呼吸器学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 20070500
• [Presentation] PTEN function in bronchioalveolar epithelium American Thoracic Society International Conference (2007)
  • Author(s): Yanagi S., Nakazato M., Suzuki A
  • Organizer: Mini-symposium
  • Place of Presentation: San Francisco
  • Year and Date: 20070500
• [Presentation] Function of PTEN in endothelial cells and NKT cells (2006)
  • Author(s): Suzuki A, Hamada K, Kishimoto H, Vanhaesbroeck B, Sasaki T
  • Organizer: 3rd Focused Meeting on PI3K Signalling and Diseases, Biochemical Society Focused Meeting
  • Place of Presentation: Bath Spa UK
  • Year and Date: 20061100
• [Presentation] Role of phosphoinositide phosphatase in neutrophil migration 3rd Focused Meeting on PI3K Signalling and Diseases (2006)
  • Author(s): Sasaki T, Nishio M, Watanabe K, Takasuga S, Sasaki J, Suzuki A
  • Organizer: Biochemical Society Focused Meeting
  • Place of Presentation: Bath Spa UK
  • Year and Date: 20061100
• [Presentation] PICT-1によるPTEN制御機構とその生理機能の解析 (2006)
  • Author(s): 佐々木雅人, 濱田浩一, 河原浩一, 佐々木雄彦, 前濱朝彦, 鈴木聡
  • Organizer: 第66回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20061000
• [Presentation] 肺胞細気管支上皮におけるPTENの機能解析 (2006)
  • Author(s): 柳重久, 岸本恕征, 河原浩一, 佐々木雄彦, 仲野徹, 中里雅光, 鈴木聡
  • Organizer: 第66回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20061000
• [Presentation] PICT-1 is involved in early embryogenesis. Role of PTEN/PI3K pathway in T cells (2006)
  • Author(s): Sasaki M, Hamada K, Kawahara K, Sasaki T, Maehama T, Suzuki A
  • Organizer: The 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: 京都
  • Year and Date: 20060600
• [Presentation] Functional analysis of a tumor suppressor gene PTEN in the urothelial carcinogenesis using a conditional PTEN-deficient mouse model (2006)
  • Author(s): Tsuruta H, Kishimoto H, Sasaki T, Shibata Y, Hamada K, Tsuchiya N, Nakano T, Habuchi T, Suzuki A
  • Organizer: 米国泌尿器科学会
  • Place of Presentation: ATLANTA
  • Year and Date: 20060500
• [Presentation] 膀胱・尿路上皮におけるPTENの機能解析 (2006)
  • Author(s): 鶴田大, 岸本恕征, 佐々木雄彦, 濱田浩一, 仲野徹, 羽渕友則, 鈴木聡
  • Organizer: 第94回日本泌尿器科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20060400
• [Presentation] (2005)
  • Author(s): 黒田聖子, 岸本恕征, 佐々木雄彦, 仲野徹, 鈴木聡
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20051200
• [Presentation] Mechanism of steatohepatitis in hepatocyte-specific Pten deficient mice, an animal model of nonalcoholic steatohepatitis (2005)
  • Author(s): Horie Y, Kataoka E, Ohshima S, Sato W, Dohmen T, Goto T, Takeuchi S, Iizuka M, Suzuki A, Watanabe S
  • Organizer: 第56回アメリカ肝臓病学会(AASLD:American Association for the Study of Liver Disease)
  • Place of Presentation: サンフランシスコ
  • Year and Date: 20051100
• [Presentation] メラノサイトにおけるptenの機能解析 (2005)
  • Author(s): 井上多恵, 濱田浩一, 岸本恕征, 佐々木雄彦, 仲野徹, 真鍋求, 鈴木聡
  • Organizer: 第64回日本癌学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20050900
• [Presentation] 膀胱・尿路上皮におけるPTENの機能解析 (2005)
  • Author(s): 鶴田大, 岸本恕征, 佐々木雄彦, 濱田浩一, 仲野徹, 羽淵友則, 鈴木聡
  • Organizer: 第64回日本癌学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20050900
• [Presentation] 発がん研究と動物モデル脂質メディエーターPTEN/pi3K経路異常による発癌と疾患 (2005)
  • Author(s): 鈴木聡, 佐々木雄彦, 濱田浩一, 岸本恕征, 佐々木雅人, 鶴田大, 羽淵友則, 井上多恵, 真鍋求, 仲野徹
  • Organizer: 第64回日本癌学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20050900
• [Presentation] Mechanism for the onset of steatohepatitis in hepatocyte-specific Pten deficient mice, an animal model of nonalcoholic steatohepatitis(NASH) (2005)
  • Author(s): Watanabe S, Horie Y, Kataoka E, Ohshima S, Sato W, Dohmen T, Goto T, Takeuchi S, Suzuki A
  • Organizer: World Congress of Gastroenterology
  • Place of Presentation: Montreal
  • Year and Date: 20050900
• [Book] 遺伝子医学MOOK(がん抑制遺伝子PTEN, 6) (2006)
  • Author(s): 柳重久、中里雅光、鈴木聡
  • Total Pages: 169-175
• [Book] 発がんの分子機構と防御(発がんモデルマウスとがん関連遺伝子の機能解析) (2006)
  • Author(s): 鈴木聡、柳沼克幸、野田哲生
  • Total Pages: 135-159
  • Publisher: 東大出版会
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/hassei/Home.html