Epigenetic alterations of GATA transcription factor genes in gastric cancers

• Project/Area Number: 19590340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: AKIYOSHI Yoshimitsu Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 講師 (80262187)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 分子病理 / メチル化 / GATA転写因子 / 胃がん / GATA4 / GATA5 / メチル化特異的PCR / メチル化特異的PCR法

Research Abstract

発生・分化に関与するGATA転写因子は6種類が単離されている。GATA4とGATA5はがん細胞でメチル化異常が見つかっているが、それらの異常と発がんとの関連性は不明である。本研究では、胃がんにおけるGATA4/5のメチル化および機能的役割について解析した。GATA4/5のメチル化異常は胃がん細胞のみならず、がん組織でも見つかった。またGATAの強制発現実験により、いくつかのがん抑制遺伝子の発現が変化し、細胞増殖抑制も起こった。以上、GATA4/5のメチル化による発現消失は胃がんの発症において重要と考えられた。

Research Products

• [Journal Article] GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer (2009)
  • Author(s): Hellebrekers DMEI, Lentjes, MHFM, van den Bosch SM, Akiyama Y, 他18名
  • Journal Title: Clinical Cancer Research (in press)
  • Peer Reviewed
• [Journal Article] DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients (2009)
  • Author(s): Yuasa Y, Nagasaki H, Akiyama Y, 他6名
  • Journal Title: International Journal of Cancer 124 Pages: 2677-2682
  • Peer Reviewed
• [Journal Article] DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients. (2009)
  • Author(s): Yuasa Y, et al.
  • Journal Title: International Journal of Cancer (in press)
  • Peer Reviewed
• [Journal Article] GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer. (2009)
  • Author(s): Hellebrekers DMEI, et al.
  • Journal Title: Clinical Cancer Research (in press)
  • Peer Reviewed
• [Journal Article] Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer (2008)
  • Author(s): Wanajo A, Sasaki A, Nagasaki H, Shimada S, Otsubo T, Owaki S, Shimizu Y, Eishi Y, Kojima K, Nakajima Y, Kawano T, Yuasa Y & Akiyama Y
  • Journal Title: Gastroenterology 135 Pages: 580-590
  • Peer Reviewed
• [Journal Article] miRNA発現プロファイル解析による癌に診断への応用 (2008)
  • Author(s): 秋山好光, 湯浅保仁
  • Journal Title: 実験医学 26 Pages: 173-178
• [Journal Article] SOX2 is frequently down-regulated in gastric cancers and inhibits cell growth through cell cycle arrest and apoptosis (2008)
  • Author(s): Otsubo T, Akiyama Y, Yanagihara K & Yuasa Y
  • Journal Title: British Journal of Cancer 98 Pages: 824-831
  • Peer Reviewed
• [Journal Article] IQGAP2 inactivation through aberrant promoter methylation and promotion of invasion in gastric cancer cells (2008)
  • Author(s): Jin S-H, Akiyama Y, Fukamachi H, Yanagihara K, Akashi T & Yuasa Y
  • Journal Title: International Journal of Cancer 122 Pages: 1040-1046
  • Peer Reviewed
• [Journal Article] Methylation of the calcium channel-related gene, CACNA2D3. is frequent and a poor prognostic factor in gastric cancer. (2008)
  • Author(s): Wanajo A, et al.
  • Journal Title: Gastroenterology 135 Pages: 580-590
  • Peer Reviewed
• [Journal Article] miRNA発現プロファイル解析による癌に診断への応用. (2008)
  • Author(s): 秋山好光, 湯浅保仁
  • Journal Title: 実験医学 26 Pages: 173-178
• [Journal Article] IQGAP2 inactivation through aberrant promoter methylation and promotion of invasion in gastric cancer cells. (2008)
  • Author(s): Jin S-H, Akiyama Y, et. al.
  • Journal Title: International Journal of Cancer 122 Pages: 1040-1046
  • Peer Reviewed
• [Journal Article] SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis. (2008)
  • Author(s): Otsubo T, Akiyama Y, et. al.
  • Journal Title: Brotish Journal of Cancer 98 Pages: 824-831
  • Peer Reviewed
• [Journal Article] Transciption factor SOX2 up-regulates stomach-specific pepsinogen A gene expression (2007)
  • Author(s): Tani Y, Akiyama Y, Fukamachi H, Yanagihara K & Yuasa Y
  • Journal Title: Journal of Cancer Research and Clinical Oncology 133 Pages: 263-269
  • Peer Reviewed
• [Journal Article] Dual blockade of the Hedgehog and ERK1/2 pathways coordinately decreases proliferation and survival of cholangiocarcinoma cells (2007)
  • Author(s): Jinawath A, Akiyama Y, Sripa B & Yuasa Y
  • Journal Title: Journal of Cancer Research and Clinical Oncology 133 Pages: 271-278
  • Peer Reviewed
• [Journal Article] Transcription factor SOX2 up-regulates stomach-specific pepsinogen Agene expression. (2007)
  • Author(s): Tani Y, Akiyama Y, et. al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology 133 Pages: 263-269
  • Peer Reviewed
• [Journal Article] Dual blockade of the Hedgehog and ERK1/2 pathways coordinately decreases proliferation and survival of cholangiocarcinoma cells. (2007)
  • Author(s): Jinawath A, Akiyama Y, et. al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology 133 Pages: 271-278
  • Peer Reviewed
• [Presentation] Tnvolvement of epigenetically silenced microRNA-181c in gastric carcinogenesis (2009)
  • Author(s): Akiyama Y, 他
  • Organizer: 9^<th> Korea-Japan Symposium on Cancer and Ageing Research
  • Place of Presentation: Damvang, 韓国
  • Year and Date: 2009-03-12
• [Presentation] Involvement of epigenetically silenced microRNA-181c in gastriccarcinogenesis. (2009)
  • Author(s): Akiyama Y, 他.
  • Organizer: 9^<th> Korea-Japan Symposium on Cancer and Ageing Research.
  • Place of Presentation: Damyang, 韓国
  • Year and Date: 2009-03-12
• [Presentation] 胃がんにおける転写関連遺伝子GATA4/5のメチル化異常と機能解析 (2008)
  • Author(s): 秋山好光, 他
  • Organizer: BMB2008第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 胃がんにおける転写関連遺伝子GATA4/5のメチル化異常と機能解析. (2008)
  • Author(s): 秋山好光, 他.
  • Organizer: BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 胃癌におけるマイクロRNA-126によるSOX2発現抑制. (2008)
  • Author(s): 大坪武史, 他.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] miR-9は消化管がん細胞においてCDX2発現を抑える. (2008)
  • Author(s): Rotkrua Pichayanoot, 他.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] 胃がんにおけるmiRNA-181cのDNAメチル化による発現低下とNOTCHシグナルの調節. (2008)
  • Author(s): 橋本裕, 他.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] 胃がん細胞における転写因子GATA5の標的遺伝子の解析 (2008)
  • Author(s): 秋山好光, 他
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 胃がん細胞における転写因子GATA5の標的遺伝子の解析. (2008)
  • Author(s): 秋山好光, 他.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 胃がん発症における電位依存性カルシウムチャンネル関連遺伝子のメチル化 (2008)
  • Author(s): 秋山好光, 他
  • Organizer: 第2回日本エピジェネティクス研究会年会
  • Place of Presentation: 三島
  • Year and Date: 2008-05-10
• [Presentation] 胃がん発症における電位依存性カルシウムチャンネル関連遺伝子のメチル化. (2008)
  • Author(s): 秋山好光, 他.
  • Organizer: 第2回日本エピジェネティクス研究会年会
  • Place of Presentation: 三島
  • Year and Date: 2008-05-10
• [Presentation] 胃がんにおけるマイクロRNA発現異常とDNAメチル化との関連. (2008)
  • Author(s): 橋本裕, 他.
  • Organizer: 第2回日本エピジェネティクス研究会年会
  • Place of Presentation: 三島
  • Year and Date: 2008-05-09
• [Presentation] Promoter hyper methylation of the calcium channel-related gene, CACNA2D3, is frequent and an independently poor prognostic factor in gastric carcinomas (2008)
  • Author(s): Akiyama Y, 他
  • Organizer: AACR 99th Annual Meeting 2008
  • Place of Presentation: San Diego, 米国
  • Year and Date: 2008-04-15
• [Presentation] Promoter hypermethylation of the calcium channel-related gene, CACNA2D3, is frequent and an independently poor prognostic factor in gastric carcinomas. (2008)
  • Author(s): Akiyama Y, 他.
  • Organizer: AACR 99th Annual Meeting 2008
  • Place of Presentation: San Diego, 米国
  • Year and Date: 2008-04-15
• [Presentation] SOX2, frequently down-regulated in gastric cancers, inhibits cell growth and its DNA hypermethylation is associated with poor prognosis in gastric cancer patients. (2008)
  • Author(s): Otsubo T, 他.
  • Organizer: AACR 99th Annual Meeting 2008
  • Place of Presentation: San Diego, 米国
  • Year and Date: 2008-04-15
• [Presentation] Hypermethylation of GATA4 and GATA5 transcription factor genes in gastric cancer. (2007)
  • Author(s): Akiyama Y, Yuasa Y.
  • Organizer: The 12th Korea-Japan Cancer Research Workshop
  • Place of Presentation: 札幌
  • Year and Date: 2007-12-22
• [Presentation] Hypermethylation of GATA4 and GATA5 transcription factor genes in gastric cancer (2007)
  • Author(s): Akiyama Y, 他
  • Organizer: The 12^<th> Korea-Japan Cancer Research Workshop
  • Place of Presentation: 札幌
  • Year and Date: 2007-12-02
• [Presentation] Expression-analysis of microRNA in gastric cancer. (2007)
  • Author(s): 和田りえ、秋山好光、他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Relationship between DNA methylation and epidemiological factors in gastric cancer patients. (2007)
  • Author(s): 湯浅保仁、長崎弘美、秋山好光、他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Frequent methylation of GATA4 and GATA5 transcription factor genes in gastric cancer (2007)
  • Author(s): 秋山好光, 他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Frequent methylation of GATA4 and GATA5 transcription. factor genes in gastric cancer. (2007)
  • Author(s): 秋山好光、他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Epigenetic silencing of SOX2 by DNA methylation in gastric cancers. (2007)
  • Author(s): 大坪武史、秋山好光、湯浅保仁.
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] GATA4 and GATA5 transcription factor genes were frequently silenced by methylation in gastric cancer (2007)
  • Author(s): Akiyama Y, 他
  • Organizer: The 8^<th> Korea-Japan Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] GATA4 and GATA5 transcription factor genes were frequently silenced by methylation in gastric cancer. (2007)
  • Author(s): Akiyama Y、他
  • Organizer: The 8th Korea-Japan Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Sox2, epigenetically silenced in gastric cancers, inhibits growth through cell cycle arrest and apoptosis. (2007)
  • Author(s): Otsubo T, Akiyama Y, 他
  • Organizer: The 8th Korea-Japan Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] IQGAP2 inactivation through aberrant promoter methylation and promotion of invasion in gastric cancer cells. (2007)
  • Author(s): Jin S-H, Akiyama Y, 他
  • Organizer: The 8th Korea-Japan Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] 胃がんにおける転写関連遺伝子GATA4/5のメチル化の解析 (2007)
  • Author(s): 秋山好光, 他
  • Organizer: 第14回日本がん予防学会・第8回日本がん分子疫学研究会・第30回日本がん疫学研究会合同大会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-13
• [Presentation] 胃がんにおける転写関連遺伝子GATA4/5のメチル化の解析. (2007)
  • Author(s): 秋山好光、他
  • Organizer: 第14回日本がん予防学会・第8回日本がん分子疫学研究会・第30回日本がん疫学研究会合同大会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-13
• [Presentation] 胃がんにおけるメチル化異常とエピジェネティクス疫学. (2007)
  • Author(s): 湯浅保仁、長崎弘美、秋山好光、他
  • Organizer: 第14回日本がん予防学会・第8回日本がん分子疫学研究会・第30回日本がん疫学研究会合同大会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-13
• [Presentation] 転写因子GATA-5の遺伝子プロモーター領域の解析 (2007)
  • Author(s): 秋山好光, 他
  • Organizer: 第1回日本エピジェネティクス研究会年会
  • Place of Presentation: 大阪
  • Year and Date: 2007-06-15
• [Presentation] 転写因子GATA-5の遺伝子プロモーター領域の解析. (2007)
  • Author(s): 秋山好光、他
  • Organizer: 第1回日本エピジェネティクス研究会年会
  • Place of Presentation: 大阪
  • Year and Date: 2007-06-15
• [Presentation] Loss of transcription factor GA TA-4/-5 by hypermethylation correlated with progression of gastric carcinomas (2007)
  • Author(s): Wen X-Y, Akiyama Y, 他
  • Organizer: AACR 97^<th> Annual Meeting
  • Place of Presentation: Los Angeles, 米国
• [Presentation] Sox2 inhibits growth of gastric epithelial cell lines through cell cycle arrest and apoptosis. (2007)
  • Author(s): Otsubo T, Akiyama Y. Yuasa Y.
  • Organizer: AACR (American Association for Cancer research)97th Annual Meeting
  • Place of Presentation: Los Angeles,米国
• [Presentation] Loss of transcription factor GATA-4/-5 by hypermethylation correlated with progression of gastric carcinomas. (2007)
  • Author(s): Wen X-Y、Akiyama Y, 他
  • Organizer: AACR 97th Annual Meeting
  • Place of Presentation: Los Angeles,米国
• [Book] バイオ実験誰もがつまずく失敗&ナットク解決法 (2008)
  • Author(s): 秋山好光(共著)
  • Total Pages: 236
  • Publisher: 羊土社