Regulation of apoptosis and autophagy under stress conditions and cancer progression

• Project/Area Number: 19590388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: INOUE Hirokazu Shiga University of Medical Science, 医学部, 准教授 (30176440)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 癌抑制遺伝子 / アポトーシス / オートファジー

Research Abstract

我々が分離したDrs遺伝子は悪性腫瘍発生に癌抑制遺伝子として働く。本研究では、Drsノックアウト細胞を用いてDrsが増殖因子枯渇などのストレス環境下でのアポトーシス(細胞死)やオートファジー(自食作用)の制御に関わっていることを明らかにした。またDrsはウイルス増殖抑制にも関与することを見出した。これらの結果から、Drsが発癌抑制だけでなく、もっと広く生体防御に重要な役割をはたしていることがわかった。

Research Products

• [Journal Article] Downregulation of drs tumor suppressor gene in highly malignant human pulmonary neuroendocrine tumors (2009)
  • Author(s): Shimakage, M., Kodama, K., Kawahara, K.,Kim, C.J., Ikeda, Y., Yutsudo, M. and Inoue, H.
  • Journal Title: Oncol. Rep 21 Pages: 1367-1372
  • Peer Reviewed
• [Journal Article] Cyclin D1 downregulation is important for permanent cell cycle exit and initiation of differentiation induced by anchorage-deprivation in human keratinocytes (2009)
  • Author(s): Nishi, K., Inoue, H., Schnier, J. B. and Rice, R. H.
  • Journal Title: J. Cell. Biohem 106 Pages: 63-72
  • Peer Reviewed
• [Journal Article] Cyclin D1 downregulation is important for permanent cell cycle exit and initiation of differentiation induced by anchorage-deprivation in human keratinocytes (2009)
  • Author(s): Nishi, K., Inoue, H., Schnier, J. B., Rice, R. H.
  • Journal Title: Journal of Cellular Biohemistry 106 Pages: 63-72
  • Peer Reviewed
• [Journal Article] Downregulation of drs tumor suppressor gene in highly malignant human pulmonary neuroendocrine tumors (2009)
  • Author(s): Shimakage, M., Kodama, K., Kawahara, K., Kim, C. J., Ikeda, Y., Yutsudo, M., Inoue, H.
  • Journal Title: Oncology Reports (In press)
  • Peer Reviewed
• [Journal Article] Cyclin D1b variant prpmotes cell invasiveness independent of binding to CDK in human bladder cancer cells (2009)
  • Author(s): Kim, C. J., Nishi, K., Isono, T., Okuyama, Y., Tambe, Y., Okada, Y., Inoue, H.
  • Journal Title: Molecular Carcinogenesis (In press)
  • Peer Reviewed
• [Journal Article] The Drs tumor suppressor is involved in the maturation process of autophagy induced by low serum (2009)
  • Author(s): Tambe, Y., Yamamoto, A., Isono, T., Chano, T., Fukuda, M., Inoue, H.
  • Journal Title: Cancer Letters (In press)
  • Peer Reviewed
• [Journal Article] Live imaging by time-lapse microscopy can more clearly evaluate the anti-apoptptic state of primary hepatocytes isolated from the Drs knockout mouse (2008)
  • Author(s): Fukumoto, K., Wang, B., Hikosaka, K., Noritake, H., Shibata, K., Inoue, H., Suzuki, A., Inaba, K., Sakaguchi, T.,Suzuki, S., Konno, H. and Miura, N.
  • Journal Title: Akita J. Med. 35 Pages: 231-237
  • Peer Reviewed
• [Journal Article] Role of alternative splicing of periostin in human bladder carcinogenesis (2008)
  • Author(s): Kim, C.J., Isono, T., Tambe, Y., Chano,T., Okabe, H., Okada, Y., and Inoue, H.
  • Journal Title: Int. J. Oncol 32 Pages: 161-169
  • Peer Reviewed
• [Journal Article] Role of alternative splicing of periostin in human bladder carcinogenesis (2008)
  • Author(s): C. J. Kim, et. al.
  • Journal Title: Int. J. Oncol. 32 Pages: 161-169
  • Peer Reviewed
• [Journal Article] Suppression of viral replication by stress-inducible GADD34 protein via the mammalian serine/threonine protein kinase mTOR pathway (2007)
  • Author(s): Minami, K., Tambe, Y., Watanabe, R., Isono, T., Haneda, M., Isobe, K.,Kobayashi, K., Hino, O., Okabe, H., Chano,T. and Inoue, H.
  • Journal Title: J. Virol 81 Pages: 11106-11115
  • Peer Reviewed
• [Journal Article] GADD34 induces p21 expression and cellular senescence (2007)
  • Author(s): Minami, K., Inoue, H., Terashita, T.,Kawakami, T., Watanabe, R., Haneda, M.,Isobe, K., Okabe, H. and Chano, T.
  • Journal Title: Oncol. Rep. 7 Pages: 1481-1485
  • Peer Reviewed
• [Journal Article] Down-regulation of drs mRNA is associated with the progression of adult T-cell leukemia/1ymphoma (2007)
  • Author(s): Shimakage, M., Inoue, N., Oshima, K., Kawahara, K., Yamamoto, N., Oka, T., Tambe,Y., Yasui, K., Matsumoto, K., Yutsudo, M. and Inoue, H.
  • Journal Title: Int. J. Oncol 30 Pages: 1343-1348
  • Peer Reviewed
• [Journal Article] GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress (2007)
  • Author(s): Watanabe, R., Tambe,Y., Inoue, H.,Isono, T., Haneda, M., Isobe, K.,Kobayashi. T., Hino, O., Okabe, H. and Chano, T
  • Journal Title: Int.J. Mol. Med. 19 Pages: 475-483
  • Peer Reviewed
• [Journal Article] Tumor prone phenotype of mice deficient in a novel apoptosis-inducing gene (2007)
  • Author(s): Tambe, Y., Yoshioka-Yamashita, A., Mukaisho, K., Haraguchi, S., Chano, T., Isono, T., Kawai, T., Suzuki, Y., Kushima, R., Hattori, T., Goto, M., Yamada, S., Kiso, M., Saga, Y., Inoue, H.
  • Journal Title: drs. Carcinogenesis 28 28 Pages: 777-784
  • Peer Reviewed
• [Journal Article] A novel tumor-related protein C7orf24, identified by proteome differential display of bladder urothelial carcinoma (2007)
  • Author(s): Kageyama, S., Iwaki, H., Inoue, H.,Isono, T., Yuasa, T., Nogawa, M., Maekawa,T., Ueda, M., Kajita, Y., Ogawa, O., Toguchida, J. and Yoshiki, T.
  • Journal Title: Proteomics Clin. Appl. 1 Pages: 192-199
  • Peer Reviewed
• [Journal Article] A novel tumor-related protein, C70rf24, identified by proteome differential display of bladder urothelial carcinoma (2007)
  • Author(s): S. Kageyama, et. al.
  • Journal Title: Proteomics Clin. Appl. 1 Pages: 192-199
  • Peer Reviewed
• [Journal Article] Tumor prone phenotype of mice deficient in a novel apoptosis-inducing gene, drs. (2007)
  • Author(s): Y. Tambe, et. al.
  • Journal Title: Carcinogenesis 28 Pages: 777-784
  • Peer Reviewed
• [Journal Article] GADD34 inhibits mammalian target of rapamycin signaling survival under bioenergetic stress (2007)
  • Author(s): R. Watanabe, et. al.
  • Journal Title: Int. J. Mol. Med. 19 Pages: 457-483
  • Peer Reviewed
• [Journal Article] Down-regulation of drs mRNA is associated with the progression of adult T-cellleukemia/lymphoma (2007)
  • Author(s): M. Shimakage, et. al.
  • Journal Title: Int. J. Oncol. 30 Pages: 1343-1348
  • Peer Reviewed
• [Journal Article] GADD34 induces p21 expression and cellular senescence (2007)
  • Author(s): K. Minami, et. al.
  • Journal Title: Oncol. Rep. 7 Pages: 1481-1485
  • Peer Reviewed
• [Journal Article] Suppression of viral replication by stress-inducible GADD34 protein via the mammalian serine/threonine protein kinase mTOR pathway (2007)
  • Author(s): K. Minami, et. al.
  • Journal Title: J. Virol. 81 Pages: 11106-11115
  • Peer Reviewed
• [Journal Article] Suppression of cell invasiveness by periostin viaTAB1/TAK1
  • Author(s): Isono, T., Kim, C. J., Ando, Y., Sakurai,H., Okada, Y. and Inoue, H.
  • Journal Title: Int. J. Oncol. (in press)
  • Peer Reviewed
• [Journal Article] The Drstumor suppressor is involved in thematuration process of autophagy induced bylow serum
  • Author(s): Tambe, Y., Yamamoto, A., Isono, T.,Chano, T., Fukuda, M. and Inoue, H.
  • Journal Title: Cancer Letters (in press)
  • Peer Reviewed
• [Journal Article] Cyclin D1b variant prpmotes cell invasiveness independent of binding to CDK in human bladder cancer cells
  • Author(s): Kim, C. J., Nishi, K., Isono, T.,Okuyama, Y., Tambe, Y., Okada, Y. and Inoue, H.
  • Journal Title: Mol .Carcinog (in press)
  • Peer Reviewed
• [Presentation] エネルギー枯渇に対するストレス応答における癌抑制遺伝子drsの役割 (2008)
  • Author(s): 旦部幸博、前田理亜、山本章嗣、茶野徳宏、井上寛一
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Splicing variant cyclin D1bによる膀胱癌細胞の悪性化促進の解析 (2008)
  • Author(s): 井上寛一、西香代子、奥山雄介、旦部幸博、岡田裕作、礒野高敬、金哲將
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Periostinによる癌の浸潤・転移抑制機構の解析 (2008)
  • Author(s): 礒野高敬, 金哲將, 安藤幸宏, 櫻井宏明, 山本章嗣, 井上寛一
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] RB1CC1 binds and activates RB1 promoter (2008)
  • Author(s): Kaichiro Ikebuchi, Tokuhiro Chano, Takahiro Isono, Hirokazu Inoue, Hidetoshi Okabe
  • Organizer: 第67回日本癌学会ワークショップ
  • Place of Presentation: 名古屋
• [Presentation] Periostin associates with TAB1 toactivate TAK1 and suppresses cell invasiveness (2008)
  • Author(s): Takahiro Isono, Chul Jang Kim, Hiroaki Sakurai, Yusaku Okada, Hirokazu Inoue
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Cyclin D1b variant enhances cell invasiveness of human bladder cancer cells (2008)
  • Author(s): Chul Jang Kim, Takahiro Isono, YukihiroTambe, Yusaku Okada, Hirokazu Inoue
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Regulation of autophagy maturation by the interaction of Drs tumor suppressor and Rab24 (2008)
  • Author(s): Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano, Hirokazu Inoue
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Regulation of autophagy maturation by the interaction of Drstumor suppressor and Rab24 (2008)
  • Author(s): Tambe, Y., Isono, T., Chano, T., Inoue, H.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Periostin associates with TAB1 to activate TAK1 and suppresses cell invasiveness (2008)
  • Author(s): Isono, T., Kim, C. J., Sakurai, H., Okada, Y. Inoue, H.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Splicing variant cyclin D1 bによる膀胱癌細胞の悪性化促進の解析 (2008)
  • Author(s): 井上寛一, 西香代子, 奥山雄介, 旦部幸博, 岡田裕作, 礒野高敬, 金哲將
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] RB1CC1 はhSNF5, p53と転写因子複合体を形成し、RB1,p16,p21の転写を促すことにより、RB経路を総合的に増強する (2007)
  • Author(s): 茶野 徳宏、池淵 嘉一郎、礒野 高敬、井上 寛一
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] ウイルス感染防御におけるストレス応答蛋白GADD34とTSC/mTOR経路の役割 (2007)
  • Author(s): 井上 寛一、南 佳ほり、旦部 幸博、礒野 高敬、渡部 亮介、磯部 健一、樋野 興夫、茶野 徳宏
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Stress-inducible GADD34 interacts with TSC1/2 to suppress mTOR signaling patyhway (2007)
  • Author(s): Hirokazu Inoue, Kahori Minami, Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] An apoptosis inducing tumor suppresser, Drs, interacts with Rab24 and regulates the maturation process of autophagy (2007)
  • Author(s): Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano, Hirokazu Inoue
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Roles of stress-inducible GADD34 for cell survival in energy depletion and cellular senescense (2007)
  • Author(s): Kahori Minami, Hirokazu Inoue, Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Down-regulation of drs tumor suppressor gene in neuroendocrine tumors of the lung (2007)
  • Author(s): Misuzu Shimakage, Ken Kodama, Kunimitsu Kawahara, Hirokazu Inoue
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] RB1CC1 enhances RB pathway in cooperation with hSNF5 and p53 (2007)
  • Author(s): Kaichiro Ikebuchi, Tokuhiro Chano, Takahiro Isono, Hirokazu Inoue, Hidetoshi Okabe
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Periostin activates TAKI and Suppresses cell invasiveness (2007)
  • Author(s): Takahiro Isono, Chul Jang Kim, Hiroaki Sakurai, Yusaku Okada, Hirokazu Inoue
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] RB1CC1はhSNF5, p53と転写因子複合体を形成し、RB1, p16, p21の転写を促すことにより、RB経路を総合的に増強する (2007)
  • Author(s): 茶野徳宏、池淵嘉一郎、礒野高敬、井上寛一
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ウイルス感染防御におけるストレス応答蛋白GADD34とTSC/mTOR 経路の役割 (2007)
  • Author(s): 井上寛一、南佳ほり、旦部幸博、礒野高敬、渡部亮介、磯部健一、樋野興夫、茶野徳宏
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] An apoptosis inducing tumor suppressor, Drs, interacts with Rab24 and regulates thematuration process of autophagy (2007)
  • Author(s): Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano, Hirokazu Inoue
  • Organizer: 第66回日本癌学会ワークショップ
  • Place of Presentation: 横浜
• [Presentation] RB1CC1 enhances RB pathway in cooperation with hSNF5 and p53 (2007)
  • Author(s): Kaichiro Ikebuchi, Tokuhiro Chano,Takahiro Isono, Hirokazu Inoue, Hidetoshi Okabe
  • Organizer: 第66回日本癌学会ワークショップ
  • Place of Presentation: 横浜
• [Presentation] Roles of stress-inducible GADD34 for cell survival in energy depletion and cellular senescense (2007)
  • Author(s): Kahori Minami, Hirokazu Inoue,Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano
  • Organizer: 第66回日本癌学会ワークショップ
  • Place of Presentation: 横浜
• [Presentation] Stress-inducible GADD34 interactswith TSC1/2 to suppress mTOR signaling patyhway (2007)
  • Author(s): Hirokazu Inoue, Kahori Minami,Yukihiro Tambe, Takahiro Isono, Tokuhiro Chano
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Analysis of oncogenic activities of cyclin D1b variant in human bladder cancer cells (2007)
  • Author(s): Chul Jang Kim, Takahiro Isono,Yukihiro Tambe, Yusaku Okada, Hirokazu Inoue
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Down-regulation of drs tumor suppressor gene in neuroendocrine tumors of the lung (2007)
  • Author(s): Misuzu Shimakage, Ken Kodama, Kunimitsu Kawahara, Hirokazu Inoue
  • Organizer: 第66 回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Periostin activates TAK1 and Suppresses cell invasiveness (2007)
  • Author(s): Takahiro Isono, Chul Jang Kim, Hiroaki Sakurai, Yusaku Okada, Hirokazu Inoue
  • Organizer: 第66 回日本癌学会総会
  • Place of Presentation: 横浜