Identification of new therapeutic target molecules and development of diagnostic markers for malignant mesothelioma

• Project/Area Number: 18390245
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: SEKIDO Yoshitaka Aichi Cancer Center Research Institute, 分子腫癌学部, 部長 (00311712)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,020,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,820,000); Fiscal Year 2008: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2007: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
• Keywords: 胸膜疾患学 / 中皮腫 / ゲノム / がん遺伝子 / 腫瘍抑制遺伝子 / 染色体異常 / 染色体

Research Abstract

悪性中皮腫の特徴的な遺伝子異常を同定するために網羅的なゲノム解析を行った。従来報告されている異常に加え、複数の新規の染色体・遺伝子異常を明らかにした。JUNやYAP遺伝子は中皮腫における重要ながん遺伝子であること、また染色体16番に新たながん抑制遺伝子が存在する可能性が示唆された。PTEN遺伝子は一部の中皮腫で不活化しており、細胞レベルにおいてがん抑制効果を確認した。本研究成果は悪性中皮腫の新規治療法や診断マーカーの開発への大きな基盤になるものと考えられた。

Research Products

• [Journal Article] Activation of the PI3K-AKT pathway in human malignant mesothelioma cells (2009)
  • Author(s): Suzuki Y, Murakami H, Kawaguchi K, Taniguchi T, Fujii M, Shinjo K, Kondo Y, Osada H, Shimokata K, Horio Y, Hasegawa Y, Hida T, Sekido Y
  • Journal Title: . Mol. Med. Rep. 2 Pages: 181-188
  • Peer Reviewed
• [Journal Article] JBIR-23 and -24, novel anticancer agents from Streptomyces sp. AK-AB27 (2009)
  • Author(s): Motohashi K, Hwang J-H, Sekido Y, Takagi M, Shin-ya K
  • Journal Title: Org. Lett. 11 Pages: 285-288
  • Peer Reviewed
• [Journal Article] Activation of the PI3K-AKT pathway in human malignant Mesothelioma cells (2009)
  • Author(s): Suzuki Y
  • Journal Title: Mol. Med. Reports 2 Pages: 181-188
  • Peer Reviewed
• [Journal Article] YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation (2008)
  • Author(s): Yokoyama T, Osada H, Murakami H, Tatematsu Y, Taniguchi T, Kondo Y, Yatabe Y, Hasegawa Y, Shimokata K, Horio Y, Hida T, Sekido Y
  • Journal Title: Carcinogenesis 29 Pages: 2139-2146
  • Peer Reviewed
• [Journal Article] Lysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2 (2008)
  • Author(s): Yamada T, Yano S, Ogino H, Ikuta K, Kakiuchi S, Hanibuchi M, Kanematsu T, Taniguchi T, Sekido Y, Sone S
  • Journal Title: Cancer Sci. 99 Pages: 1603-1610
  • NAID: 10024009864
  • Peer Reviewed
• [Journal Article] Molecular biology of malignant mesothelioma (2008)
  • Author(s): Sekido Y
  • Journal Title: Environ. Health Prev. Med. 13 Pages: 65-70
  • NAID: 10026956757
• [Journal Article] YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation (2008)
  • Author(s): Yokoyama T
  • Journal Title: Carcinogenesis 29 Pages: 2139-2146
  • Peer Reviewed
• [Journal Article] Lysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2 (2008)
  • Author(s): Yamada T
  • Journal Title: Cancer Sci. 99 Pages: 1603-1610
  • Peer Reviewed
• [Journal Article] Genomic pro filing of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32 (2007)
  • Author(s): Taniguchi T, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y
  • Journal Title: Cancer Sci. 98 Pages: 438-446
  • Peer Reviewed
• [Journal Article] Genomic profiling of malignant pleural mesothelioma with array-based comparative hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32 (2007)
  • Author(s): Taniguchi T. et al.
  • Journal Title: Cancer Science 98 Pages: 438-446
• [Journal Article] Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells
  • Author(s): Kawaguchi K, Murakami H, Taniguchi T, Fujii M, Kawata S, Fukui T, Kondo Y, Osada H, Usami N, Yokoi K, Ueda Y, Yatabe Y, Ito M, Horio Y, Hida T, Sekido Y
  • Journal Title: Carcinogenesis (in press)
  • Peer Reviewed
• [Presentation] 悪性中皮腫細胞のシグナル伝達系異常 (2008)
  • Author(s): 関戸好孝
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-14
• [Presentation] 悪性中皮腫細胞のシグナル伝達異常 (2008)
  • Author(s): 関戸好孝
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-14
• [Presentation] 悪性胸膜中皮腫におけるMETの活性化 (2008)
  • Author(s): 川口晃司, 村上秀樹, 谷口哲朗, 藤井万紀子, 近藤豊, 長田啓隆, 関戸好孝
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 中皮腫細胞株における遺伝子発現プロファイリング (2008)
  • Author(s): 村上秀樹, 谷口哲郎, 川口晃司, 藤井万紀子, 近藤豊, 長田啓隆, 関戸好孝
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Establishment and characterization of new malignant pleural mesothelioma cell lines from Japanese patients (2008)
  • Author(s): Taniguchi T, Murakami H, Fujii M, Usami N, Yokoi K, Sekido Y
  • Organizer: The 9^<th> International conference of the International mesothelioma interest group
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2008-09-26
• [Presentation] 悪性胸膜中皮腫におけるDNAメチル化標的遺伝子の解析とその診断への応用 (2008)
  • Author(s): 新城恵子, 近藤豊, 後藤康洋, 近藤征史, 長谷川好, 下方薫, 関戸好孝
  • Organizer: 第48回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-17
• [Presentation] Activation of receptor tyrosine kinase c-Met in malignant pleural mesothelioma cells (2008)
  • Author(s): Kawaguchi K, Murakami H, Suzuki Y, Taniguchi T, Yokoi K, Sekido Y
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-04-15
• [Presentation] Activation of PI3K/AKT signaling pathway in malignant pleural mesothelioma cells (2008)
  • Author(s): Suzuki Y, Murakami H, Kawaguchi K, Taniguchi T, Hasegawa Y, Shimokata K, Sekido Y
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-04-14
• [Presentation] 悪性中皮腫細胞株に対するTGF-betaシグナルの影響 (2008)
  • Author(s): 藤井万紀子, 谷口哲郎, 村上秀樹, 長田啓隆, 関戸好孝
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 悪性胸膜中皮腫におけるPI3K/AKT経路、PTEN遺伝子変異の検討 (2007)
  • Author(s): 鈴木裕太郎, 村上秀樹, 川口晃司, 谷口哲郎, 長谷川好規, 下方薫, 関戸好孝
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-09
• [Presentation] 悪性中皮腫細胞のゲノム異常 (2007)
  • Author(s): 関戸好孝
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-09
• [Presentation] 悪性中皮腫細胞のゲノム異常 (2007)
  • Author(s): 関戸 好孝
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2007-11-09
• [Presentation] 悪性胸膜中皮腫においてDNAメチル化により制御されるがん抑制遺伝子の網羅的解析 (2007)
  • Author(s): 後藤康洋, 近藤豊, 新城恵子, 谷口哲郎, 近藤征史, 今泉和良, 長谷川好規, 下方薫, 関戸好孝
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-08
• [Presentation] 悪性胸膜中皮腫におけるHGF/METの発現と活性化の解析 (2007)
  • Author(s): 川口晃司, 村上秀樹, 鈴木裕太郎, 谷口哲郎, 横井香平, 関戸好孝
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-08
• [Presentation] 日本人悪性胸膜中皮腫患者由来の新しい中皮腫細胞株の樹立と解析 (2007)
  • Author(s): 谷口哲郎, 村上秀樹, 川口晃司, 鈴木裕太郎, 横井香平, 関戸好孝
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-08
• [Presentation] YAP1は悪性胸膜中皮腫の増殖を促進し、NF2腫瘍抑制遺伝子で機能阻害される (2007)
  • Author(s): 横山俊彦, 長田啓隆, 村上秀樹, 立松義朗, 谷口哲郎, 近藤豊, 樋田豊明, 長谷川好規, 下方薫, 関戸好孝
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-08
• [Presentation] がん遺伝子YAP1は悪性胸膜中皮腫の増殖に関与し、がん抑制遺伝子NF2で機能阻害される (2007)
  • Author(s): 横山俊彦, 長田啓隆, 村上秀樹, 立松義朗, 谷口哲郎, 近藤豊, 樋田豊明, 下方薫, 関戸好孝
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Ectopic Merlin expression inhibits the growth of NF2-difficient cells with the distinct change of gene expression pattern (2007)
  • Author(s): 村上秀樹, 谷口哲郎, 川口晃司, 鈴木裕太郎, 近藤豊, 長田啓隆, 関戸好孝
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] 胸膜中皮腫に対するアムルビシノールとシクロオキシゲナーゼ2阻害剤の増殖抑制効果 (2007)
  • Author(s): 樋田豊明, 朴智栄, 小川紫都, 清水淳市, 堀尾芳嗣, 吉田公秀, 谷田部恭, 谷口哲朗, 関戸好孝
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Genomic pro filing of malignant pleural mesothelioma with array-based comparat ive genomic hybridization (2007)
  • Author(s): Taniguchi T, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y
  • Organizer: 12^<th> World Conference on Lung Cancer
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2007-09-05
• [Presentation] Genomic pro filing of malignant pleural mesothelioma with array-based comparat ive genomic hybridization shows frequent nonrandom chromosomal alteration regions including JUN amplification on 1p32 (2007)
  • Author(s): Taniguchi T, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y
  • Organizer: AACR
  • Place of Presentation: Los Angels, USA
  • Year and Date: 2007-04-17
• [Presentation] Genome wide analyses for aberrant DNA methylation observed in malignant pleural mesothelioma (2007)
  • Author(s): Goto Y, Kondo Y, Gao D, Toyota M, Suzuki H, Ito M, Yokoyama T, Taniguchi T, Osada H, Murakami H, Tokino T, Imai K, Hasegawa Y, Shimokata K, Sekido Y
  • Organizer: AACR
  • Place of Presentation: Los Angels, USA
  • Year and Date: 2007-04-16
• [Presentation] Genetic and epigenetic alterations in newly established malignant pleuralmesothelioma cell lines (2007)
  • Author(s): Sekido Y, Murakami H, Kondo Y, Taniguchi T, Yokoyama T, Goto Y, Fukui T, Seto M, Osada H, Hida T
  • Organizer: 7^<th> Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
  • Place of Presentation: Waikoloa, USA
  • Year and Date: 2007-01-22
• [Presentation] Establishment and characterization of four malignant pleura! mesothelioma cell lines from Japanese patients (2006)
  • Author(s): Usami N, Fukui T, Kondo M, Taniguchi T, Yokoi K, Shimokata K, Hida T, Sekido Y
  • Organizer: The 8^<th> International Conference of the International Mesothelioma Interest Group
  • Place of Presentation: Chicago, USA
  • Year and Date: 2006-10-20
• [Presentation] Array CGH法を用いた悪性胸膜中皮腫の網羅的ゲノム解析 (2006)
  • Author(s): 谷口哲朗, シバスンダラム カルナン, 福井高幸, 横山俊彦, 田川博之, 光冨徹哉, 堀尾芳嗣, 樋田豊明, 谷田部恭, 瀬戸加大, 関戸好孝
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-29
• [Presentation] 悪性胸膜中皮腫における染色体11q22増幅領域の解析 (2006)
  • Author(s): 横山俊彦, 長田啓隆, 谷口哲郎, 近藤豊, 福井高幸, 樋田豊明, 谷田部恭, 瀬戸加大, 下方薫, 関戸好孝
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-28
• [Presentation] 日本人由来悪性胸膜中皮腫細胞株の樹立と解析 (2006)
  • Author(s): 福井高幸, 宇佐美範恭, 谷口哲郎, 横山俊彦, 樋田豊明, 関戸好孝
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-28
• [Presentation] 胸膜中皮腫に対するシクロオキシゲナーゼ(COX)阻害剤及びCOX阻害剤と抗がん剤投与によるin vitro増殖抑制効果の検討 (2006)
  • Author(s): 樋田豊明, 朴智栄, 清水淳市, 堀尾芳嗣, 吉田公秀, 谷田部恭, 関戸好孝
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-28
• [Remarks] ホームページ
  • URL: http://www.pref.aichi.jp/cancer-center/400/420/421/421-03.html
• [Remarks] アウトリーチ活動(公開講座)関戸好孝「アスベストと中皮腫」平成19年度愛知県がんセンター公開講座 2007年7月12日 愛知県がんセンター国際交流センター、名古屋
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/400/420/421/421-03.html