Molecular mechanism of hypoxia-induced genome instability in human colorectal cancer

• Project/Area Number: 21591736
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Toho University
• Principal Investigator: HEMMI Hiromichi 東邦大学, 医学部, 准教授 (90165514)
• Co-Investigator(Kenkyū-buntansha): SHIBUYA Kazutoshi 東邦大学, 医学部, 教授 (20196447) ; ARITA Michitsune 東邦大学, 医学部, 助教 (80307719) ; KOIKE Junichi 東邦大学, 医学部, 講師 (30339155)
• Co-Investigator(Renkei-kenkyūsha): KANAZAWA Shinsaku 東邦大学, 医学部, 助教 (00408767)
• Research Collaborator: LI Jie 東邦大学, 医学部, 大学院生 ; YAMADA Kanae 東邦大学, 医学部, 研究生
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 遺伝子 / 大腸がん / ゲノム不安定性 / EMAST / 発現制御 / 低酸素 / DNA修復 / GLUT1

Research Abstract

Frequency of EMAST, a phenotype of genetic instability, in Japan was approximately 60%, which is similar to USA. Down-regulation of hMSH3 by hypoxia was studied in human cell lines derived from different origins including colon. Three patterns : rapid, moderate, and none responses were observed. Moderate type was observed in cells having mutant p53.Histochemical staining of clinical samples supports that down-regulation of hMSH3 is induced by hypoxia. Transient hypoxia is not enough for generation of EMAST tumor. Repeated states of hypoxia-reoxyganation may require for induction of EMAST.

Research Products

• [Journal Article] MicroRNA-200c modulates epithelial-to-mesenchymal transition(EMT) in human colorectal cancer metastasis (2012)
  • Author(s): Hur K, Toiyama Y, Takahashi M, Koike J, Hemmi H, Balaguer F, Nagasaka T, Koi M, Boland CR, Goel A
  • Journal Title: GUT Volume: (in press)
  • Peer Reviewed
• [Journal Article] Downregulation of MutS homolog 3 by hypoxia in human colorectal cancer (2012)
  • Author(s): Li J, Koike J, Kugoh H, Arita M, Ohhira T, Kikuchi Y. Funahashi K, Takamatsu K, Boland CR, Koi M, Hemmi H
  • Journal Title: Biochim Biophys Acta Volume: 1823(4) Pages: 889-99
  • URL: http://dx.doi.org/10.1016/j.bbamcr.2012.01.017
  • Peer Reviewed
• [Journal Article] Down-regulation of MutS homolog 3 by hypoxia in human colorectal cancer (2012)
  • Author(s): Li J, Koike J, Kugoh H, Arita M, Ohhira T, Kikuchi Y, Funahashi K, Takamatsu K, Boland CR, Koi M, Hemmi H
  • Journal Title: Biochim Biophys Acta -Molecular Cell Research Volume: 1823(4) Issue: 4 Pages: 889-899
  • DOI: 10.1016/j.bbamcr.2012.01.017
  • Peer Reviewed
• [Journal Article] Effluent markers related to epithelial mesenchymal transition with adjusted values for effluent cancer antigen 125 in peritoneal dialysis patients (2011)
  • Author(s): Mizuiri S, Hemmi H, et al
  • Journal Title: Int J Nephrol Volume: 2011 Pages: 2610401-5
  • DOI: 10.4061/2011/261040
  • Peer Reviewed
• [Journal Article] Factors regulating angiotensin-converting enzyme 2 expression in a human proximal tubular cell line HK-2. (2011)
  • Author(s): Aoki T, Hemmi H, Arita M, et al
  • Journal Title: J Med Soc Toho Volume: 58(1) Pages: 19-26
  • NAID: 40017650365
  • Peer Reviewed
• [Journal Article] Effluent markers related to epithelial mesenchymal transition with adjusted values for effluent cancer antigen 125 in peritoneal dialysis patients. (2011)
  • Author(s): Mizuiri S, Hemmi H, Arita M, et al
  • Journal Title: Int J Nephrol Volume: (in Press)
  • Peer Reviewed
• [Journal Article] Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan (2010)
  • Author(s): Yamada K, Kanazawa S, Koike J, Sugiyama H, Xu C, Funahashi K, Boland CR, Koi M, Hemmi H
  • Journal Title: Oncol Rep Volume: 23(2) Pages: 551-61
  • Peer Reviewed
• [Journal Article] Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan (2010)
  • Author(s): Yamada K, Kanazawa S, Koike J, Boland CR, Koi M, Hemmi H, 他3名
  • Journal Title: Oncol Rep 23 Pages: 551-561
  • Peer Reviewed
• [Journal Article] 14-3-3σ-dependent resistance to cisplatin (2009)
  • Author(s): Han Z, Dimas K, Tian X, Wang Y, Hemmi H, Yamada K, Kato N, Pantazis P, Ramanujam RJ, Anant S, Wyche JH, Houchen CW
  • Journal Title: Anticancer Res Volume: 29(6) Pages: 2009-2014
  • Peer Reviewed
• [Journal Article] FOLFOX therapy for advanced metastatic rectal cancer with Gibert syndrome (2009)
  • Author(s): Koike J, Funahashi K, Saito N, Shirasaka K, Hemmi H, Kaneko S, Teramoto T
  • Journal Title: J Toho Med Soc Volume: 56(1) Pages: 27-32
  • Peer Reviewed
• [Presentation] 低酸素によるhMLH1発現抑制におけるSYF2およびhnRPH1の役割 (2011)
  • Author(s): 有田通恒, 逸見仁道, 他
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-04
• [Presentation] Identification of gene loci with microsatellite repeats frequently altered in liver metastasis exhibiting moderate levels of microsatellite instability from primary CRC (2011)
  • Author(s): Garcia M, Choi C, Kim H, Koike J, Hemmi H, Li J, Nagasaka T, Boland CR, Koi M
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, IL.
  • Year and Date: 2011-05-17
• [Presentation] MicroRNA-200c/141 cluster as a control switch between epithelial-to-mesenchymal transition(EMT) and mesenchymal-to-epithelial transition(MET) in human colorectal cancer metastasis (2011)
  • Author(s): Goel A, Hemmi H, Koi M, Boland CR, et al
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, IL
  • Year and Date: 2011-05-17
• [Presentation] 低酸素によるhMLH1発現抑制時の転写因子CXXC5, SYF2およびhnRPH1の関与 (2011)
  • Author(s): 有田通恒, 李傑, 菅野新一郎, 菊池由宣, 安井明, 近藤元就, 逸見仁道
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] N-myc非増幅神経芽腫細胞におけるN-mycの役割 (2011)
  • Author(s): 李傑, 有田通恒, 柴田祐充子, 岩崎維和夫, 黒岩実, 近藤元就, 逸見仁道
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: 前橋
• [Presentation] 低酸素によるhMLH1発現抑制におけるSYF2およびhnRPH1の役割 (2011)
  • Author(s): 有田通恒, 李傑, 安井明, 近藤元就, 逸見仁道
  • Organizer: The 70th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Regulation of MMR genes and stem cell markers in hypoxia in colorectal cancer cells.(English Workshop) (2010)
  • Author(s): Li J, Arita M, Koike J, Hemmi H.
  • Organizer: The 69th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-24
• [Presentation] 大腸がん由来細胞株におけるhMSH3転写制御機構 (2010)
  • Author(s): 李傑, 有田通恒, 児井稔, 逸見仁道
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] CXXC5とSYF/p29によるhM転写制御, a zinc finger protein (2010)
  • Author(s): 有田通恒, 李傑, 菅野新一郎, 安井明, 逸見仁道
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Regulation of MMR genes and stem cell markers in hypoxia in colorectal cancer cells (2010)
  • Author(s): Li J, Arita M, Koike J, Hemmi H
  • Organizer: The 69th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka
• [Presentation] A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH1 (2010)
  • Author(s): Arita M, Li J, Yasui A, Hemmi H
  • Organizer: The 69th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka
• [Presentation] A study in regulatory mechanism of the MSH3 gene expression (2009)
  • Author(s): Li J, Min Z, Arita M, Koi M, Hemmi H
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-09
• [Presentation] Transcriptional regulation of the hMLH1 gene by CXXC5, a zinc finger protein (2009)
  • Author(s): 有田通恒, 李傑, 菅野新一郎, 安井明, 逸見仁道
  • Organizer: The 32nd Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Yokohama
• [Presentation] A study in regulatory mechanism of the MSH3 gene expression (2009)
  • Author(s): Li J, Min Z, Arita M, Koi M, Hemmi H
  • Organizer: The 32nd Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Yokohama