Elucidation of the significance of MAPK-dependent MITF activation in melanoma

• Project/Area Number: 19590321
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Keio University
• Principal Investigator: SUMIMOTO Hidetoshi Keio University, 医学部, 助教 (00306838)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: MITF / BRAF / MAPK / melanoma / DNA microarray / 悪性黒色腫 / RNAi / DNAマイクロアレイ / 分子標的 / HIVベクター

Research Abstract

悪性黒色腫細胞で活性化の見られる二種類の癌遺伝子、BRAFとMITFを標的化する治療法の有用性を検討した。各単独の抑制で細胞増殖抑制効果に対して耐性を示す複数の悪性黒色腫細胞株において、両者を同時に抑制することでより強力な抑制効果を認めた。DNAマイクロアレイ解析により、両者の遺伝子により個別にまたは共通に発現制御を受ける遺伝子発現プロフィールを作製し、悪性黒色腫に対する新規分子標的の候補を得た。

Research Products

• [Journal Article] Tumor growth suppression by adenovirus-mediated introduction of a cell growth suppressing gene tob in a pancreatic cancer model. (2009)
  • Author(s): Yanagie H, Sumimoto H, et al.
  • Journal Title: Biomed Pharmacother. 63 Pages: 275-286
  • Peer Reviewed
• [Journal Article] Tumor growth suppression by adenovirus-mediated introduction of a cell growth suppressing gene tob in a pancreatic cancer model (2008)
  • Author(s): Yanagie H, Tanabe T, Sumimoto H, Sugiyama H, Matsuda S, Nonaka Y, Ogiwara N, Sasaki K, Tani K, Takamoto S, Takahashi H, Eriguchi M.
  • Journal Title: Biomed Pharmacother Epubahead of print
  • Peer Reviewed
• [Journal Article] Dendritic cell based personalized immunotherapy based on cancer antigen research (2008)
  • Author(s): Kawakami Y, Fujita T, Kudo C, Sakurai T, Udagawa M, Yaguchi T, Hasegawa G, Hayashi E, Ueda Y, Iwata T, Wang Q, Okada S, Tsukamoto N, Matsuzaki Y, Sumimoto H.
  • Journal Title: Frontiers in Bioscience 1;13 Pages: 1952-1958
• [Journal Article] Takayanagi A, Miyashita K, Akao M, Tabata M, Tamiya G, Ohkura T, Hibi T. Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice (2008)
  • Author(s): Tomita K, Oike Y, Teratani T, Taguchi T, Noguchi M, Suzuki T, Mizutani A, Yokoyama H, Irie R, Sumimoto H
  • Journal Title: Hepatology 48 Pages: 458-473
  • Peer Reviewed
• [Journal Article] Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice. (2008)
  • Author(s): Tomita K, Sumimoto H, et al.
  • Journal Title: Hepatology 48 Pages: 458-73
  • Peer Reviewed
• [Journal Article] Development of individualized immunotherapy based on the analysis on anti-tumor immune responses to the human tumor antigens identified using immunological and genetic methods (2007)
  • Author(s): Kawakami Y, Fujita T, Kudo C, Sakurai T, Udagawa M, Hasegawa G, Ishida A, Kitagawa Y, Tanabe M, Saito M, Izumi Y, Kawamura M, Yaguchi T, Ueda Y, Hayashi E, Wang Q, Okada S, Tsukamoto N, Matsuzaki Y, Sumimoto H, Takeuchi H, Tanikawa A, Handa M, Amagai M, Kobayashi K, Ikeda Y, Azuma I, Kitajima M.
  • Journal Title: Gene Therapy 2007 Pages: 240-248
  • Peer Reviewed
• [Journal Article] Lentiviral vector-mediated RNAi and its use for cancer research (2007)
  • Author(s): Sumimoto H and Kawakami Y.
  • Journal Title: Future Oncol 3(6) Pages: 655-664
  • Peer Reviewed
• [Journal Article] メラノーマ細胞の免疫回避機構 (2007)
  • Author(s): 住本秀敏
  • Journal Title: 臨床免疫・アレルギー科 vol.47, No.3 Pages: 361-366
  • NAID: 40015423626
• [Journal Article] Lentiviral vector-mediated RNAi and its use for cancer research (2007)
  • Author(s): Sumimoto H, Kawakami Y
  • Journal Title: Future Oncology 3 Pages: 655-664
  • Peer Reviewed
• [Presentation] ヒト悪性黒色腫細胞株によるヒト単球由来MDSC様サブセットの誘導 (2008)
  • Author(s): 山本夏啓、住本秀敏、川村直、梅澤一夫、河上裕
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] 癌細胞におけるMAPKシグナル亢進による腫瘍免疫逃避機構の解明/ (2008)
  • Author(s): 谷口智憲、木藤健治、塚本信夫、桜井敏晴、藤田知信、持丸博史、丸山正太郎、里見良輔、井田陽介、住本秀敏、河上裕
  • Organizer: Roles of activated MAPK pathway in generation of immunosuppressive microenvironment by the production of immunosuppressive cytokines from various cancers
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] Immunosuppression by human melanomavia activated Wnt/beta-catenin signaling. (Wnt/beta-cateninシグナル亢進による悪性黒色種の免疫逃避機構の解明) (2008)
  • Author(s): 谷口智憲、木藤健治、塚本信夫、桜井敏晴、持丸博史、丸山正太郎、里見良輔、井田陽介、住本秀敏、河上裕
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Use of cultured dendritic cells for immunotherapy of cancer. (培養樹状細胞を用いた免疫療法) (2008)
  • Author(s): 河上裕、住本秀敏、工藤千恵、塚本信夫、藤田知信、桜井敏晴、谷口智憲、岩田知子、川村直
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] MCL-1 knockdown enhances 5-FU-INDUCED apoptosis in side poplation (SP) cells of gastric cancer cells. (胃癌細胞株の幹細胞におけるMyeloid cell Leukemia-1 (Mcl-1)蛋白阻害によるアポトーシス増強作用の検討) (2008)
  • Author(s): 飯塚秀子、樋口肇、住本秀敏、樺島彩乃、酒井元、泉谷幹子、山岸由幸、高石官均、河上裕、水口裕之、日比紀之
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 癌シグナル伝達異常による癌免疫逃避機構の解析 (2008)
  • Author(s): 谷口智憲、木藤健治、丸山正太郎、住本秀敏、河上裕
  • Organizer: 第28回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-03
• [Presentation] Molecular mechanismis for immuno-suppression induced by melanoma cells (2008)
  • Author(s): Yutaka Kawakami, Hidetoshi Sumimoto, Chie Kudo, Nobuo Tsukamoto, Tomonori Yaguchi
  • Organizer: 20th International Pigment Cell Conference & 5th International Melanoma Research Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2008-05-12
• [Presentation] siRNAライブラリーを用いた癌免疫回避シグナルの同定 (2008)
  • Author(s): 川村直、住本秀敏、河上裕
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] siRNAライブラリーを用いた癌免疫回避シグナルの同定 (2008)
  • Author(s): 川村直、住本秀敏、河上裕
  • Organizer: 第12回基盤的癌免疫研究会
  • Place of Presentation: 大宮、埼玉
• [Presentation] si-RNAライブラリーを用いた癌免疫回避シグナルの同定 (2008)
  • Author(s): 川村直, 住本秀敏, 河上裕
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Molecular mechanisms for generation of immunosuppressive microenvironment by cancer cells (2007)
  • Author(s): Yutaka Kawakami, Hidetoshi Sumimoto, Chie Kudo, Tomonori Yaguchi
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Induction of high IL10 producing DC by melanoma cells with altered Wnt/beta -catenin signaling (2007)
  • Author(s): Tomonori Yaguchi, Kenji Kido, Nobuo Tsukamoto, Hiroshi Mochimaru, Shotaro Maruyama, Ryosuke Satomi, Hidetoshi Sumimoto, Yutaka Kawakami
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Possible inhibition of TLR signaling by PI3K through preventing PIP2-associated TIRAP recruitment to plasma cell membrane in human dendritic cells (2007)
  • Author(s): Sumimoto, H., Takahashi, T., Kawakami, Y.
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] MITF protein levels determine the proliferation status of melanoma cells (2007)
  • Author(s): Sumimoto H, et. al.
  • Organizer: The 4th International Melanoma Congress
  • Place of Presentation: New York,USA
  • Year and Date: 2007-11-03
• [Presentation] (2007)
  • Author(s): Yutaka Kawakami, Tomonobu Fujita, Chie Kudo, Masaru Udagawa, Toshiharu Sakurai, Yoko Ueda, Tomonori Yaguchi, Hidetoshi Sumimoto
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] MCL-1 depletion by adenoviral-mediated short hairpin RNA enhances apoptosis sensitivity in gastrointestinal cancer cells (2007)
  • Author(s): Hideko Iizuka, Hajime Higuchi, Hidetoshi Sumimoto, Ayano Kabashima, Naoko Kuriyama, Gen Sakai, Motoko Izumiya, Yoshiyuki Yamagishi, Hiromasa Takaishi, Yutaka Kawakami, Hiroyuki Mizuguchi, Toshifumi Hibi
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] The proliferation of melanoma cells depends on the protein levels of MITF (2007)
  • Author(s): 住本秀敏、木藤健治、浅田咲世、岡田スターリン、谷口智憲、斎田俊雄、河上裕
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] The proliferation of melanoma cells depends on the protein levels of MITF (2007)
  • Author(s): Sumimoto H, et. al.
  • Organizer: 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 2007-10-04
• [Presentation] Role of Wnt/beta-catenin Signaling Pathway in Production of an Immunosuppressive Cytokine, IL10, by Melanoma Cells : Possible Mechanisms for Cancer Immunoescape (2007)
  • Author(s): 谷口智憲、木藤健治、塚本信夫、持丸博史、丸山正太郎、住本秀敏、河上裕
  • Organizer: 第11回基盤的癌免疫研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-11
• [Presentation] MCL-1 depletion sensitizes the apoptosis of gastrointestinal cancer cells mediated by anti-cancer drugs (2007)
  • Author(s): Hideko Iizuka, Hajime Higuchi, Hidetoshi Sumimoto, Ayano Kabashima, Naoko Kuriyama, Gen Sakai, Motoko Izumiya, Yoshiyuki Yamagishi, Hiromasa Takaishi, Yutaka Kawakami, Hiroyuki Mizuguchi, Toshifumi Hibi
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Tokyo
  • Year and Date: 2007-07-11
• [Presentation] Immunotherapy and gene therapy using viral vectors (2007)
  • Author(s): Yutaka Kawakami, Masaru Udagawa, Kenji Kido, Tomonori Yaguchi, Masahiro Toda, Chie Kudo, Hidetoshi Sumimoto
  • Organizer: The 13^<th> annual meeting of Japan Society of Gene Therapy
  • Place of Presentation: Nagoya
  • Year and Date: 2007-06-30
• [Presentation] Enhancement of human monocyte-derived dendritic cell functions by adenovirus-mediated RNA interference of STAT-3 (2007)
  • Author(s): Iwata, T., Sumimoto, H., Mizuguchi, H., Kawakami, Y.
  • Organizer: The 13^<th> annual meeting of Japan Society of Gene Therapy
  • Place of Presentation: Nagoya
  • Year and Date: 2007-06-30
• [Presentation] MITF protein levels determine the proliferation status of melanoma cells (2007)
  • Author(s): Kido, K., Sumimoto, H., Asada, S., Okada, S. M., Yaguchi, T., Saida, T., Kawakami, Y.
  • Organizer: The 13^<th> annual meeting of Japan Society of Gene Therapy
  • Place of Presentation: Nagoya
  • Year and Date: 2007-06-30
• [Presentation] レンチウイルスshRNAを用いたMITF発現抑制による悪性黒色腫細胞の増殖・浸潤の抑制 (2007)
  • Author(s): 木藤健治、住本秀敏、浅田咲世、岡田スターリン、谷口智憲、斎田俊明、河上裕
  • Organizer: 日本研究皮膚科学会第32回年次学術大会・総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-04-20
• [Presentation] MITF protein levels determine the proliferation status of melanoma cells (2007)
  • Author(s): Sumimoto, H., Kido, K., Asada, S., Okada, S. M., Yaguchi, T., Saida, T., Kawakami, Y.
  • Organizer: The 4^<th> International Melanoma Congress
  • Place of Presentation: New York, USA
• [Book] Chapter 13. The RNA silencing technology applied by lentiviral vectors in oncology. Lentivirus Gene Engineering Protocols. the 2nd edition (2009)
  • Author(s): Hidetoshi Sumimoto and Yutaka Kawakami
  • Publisher: Human Press Ed. (in press)
• [Book] Chapter 13. The RNA silencing technology applied by lentiviral vectors in oncology. Lentivirus Gene Engineering Protocols, the 2^<nd> edition (2009)
  • Author(s): Sumimoto H, Kawakami Y.
  • Publisher: Human Press(in press)
• [Patent(Industrial Property Rights)] 抗腫瘍剤 (2008)
  • Inventor(s): 住本秀敏、川村直、河上裕
  • Industrial Property Rights Holder: 慶應義塾大学
  • Industrial Property Number: 2008-166291
  • Filing Date: 2008-06-25
  • Overseas
• [Patent(Industrial Property Rights)] 抗腫瘍剤 (2008)
  • Inventor(s): 住本秀敏, 川村直, 河上裕
  • Industrial Property Rights Holder: 慶應義塾大学
  • Industrial Property Number: 2008-166291
  • Filing Date: 2008-06-25