The roles of HIF-DEC pathway on DNA repair systems in hypoxic oral cancer cells.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hiroshima University
• Principal Investigator: TANIMOTO Keiji 広島大学, 原爆放射線医科学研究所, 助教 (90335688)
• Project Period (FY): 2011 – 2013
• Keywords: Hypoxia / HIF / DEC / DNA repair / Transcription / Cancer cells

Research Abstract

In this study, we analyzed expression changes of numerous DNA repair-related genes under hypoxia, further noted that the effect of the changes to radiation sensitivities. Comprehensive gene expression analyses showed that 50 of 130 DNA repair-related genes were included in down-regulated genes under hypoxia. Among these genes we selected 6 genes and confirmed quantitative decreased expressions. Co-transfection reporter assay elucidated that DEC1 or DEC2 repressed those DNA repair-related genes promoter activities. In addition, knockdown of HIF1A or DEC2 attenuated hypoxic suppression of DNA repair-related gene expressions. Interestingly, detection and repair of DNA double-strand breaks by irradiations were inhibited in hypoxic pre-incubated cells. Moreover, knockdown of DEC2 increased radiation sensitivities in those cells. These data suggested that HIF-1-DEC pathway especially DEC2 play a pivotal role in radiation sensitivity via suppression of DNA repair gene expressions.

Research Products

• [Journal Article] Yoshio Hosoi. Mitochondria are required for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells (2013)
  • Author(s): Akinori Morita, Keiji Tanimoto, Tomoki Murakami, Takeshi Morinaga, Yoshio Hosoi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 443 Pages: 1286-1290
  • Peer Reviewed
• [Journal Article] The Krüppel-like zinc finger transcription factor, GLI-similar 1, is regulated by hypoxia-inducible factors via non-canonical mechanisms (2013)
  • Author(s): Elham Khalesi, Hideaki Nakamura, Kian Leong Lee, Andika Chandra Putra, Takahiro Fukazawa, Yumi Kawahara, Yuichi Makino, Lorenz Poellinger, Louis Yuge, Keiji Tanimoto
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 441 Pages: 499-506
  • Peer Reviewed
• [Journal Article] An association study between Hypoxia inducible Factor-1alpha (HIF-1α) polymorphisms and osteonecrosis (2013)
  • Author(s): Georgia Chachami, Alkmini KalousI, Loukia Papatheodorou, Aggeliki Lyberopoulou, Vassilis Nasikas, Keiji Tanimoto, G. Simos, K. N. Malizos, E. Georgatsou
  • Journal Title: PLOS ONE Volume: 8 Pages: e79647
  • Peer Reviewed
• [Journal Article] Interactive effects of cell therapy and rehabilitation realize the full potential of neurogenesis in brain injury model (2013)
  • Author(s): Takeshi Imura, Masaya Matsumoto, Takahiro Fukazawa, Elham Khalesi, Ya-Nan Sun, Masaaki Takeda, Hiroyuki Uwatoko, Kyosuke Nakata, Keiji Tanimoto, Teruyuki Kajiume, Yumi Kawahara, Louis Yuge
  • Journal Title: Neuroscience Letters Volume: 555 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Electrical stimulation accelerates neuromuscular junction formation through ADAM19/neuregulin/ErbB signaling in vitro (2013)
  • Author(s): Takahiro Fukazawa, Masaya Matsumoto, Takeshi Imura, Elham Khalesi, Teruyuki Kajiume, Yumi Kawahara, Keiji Tanimoto, Louis Yuge
  • Journal Title: Neuroscience Letters Volume: 545 Pages: 29-34
  • Peer Reviewed
• [Journal Article] Development of lymphoproliferative diseases by hypoxia-inducible factor-1αis associated with prolonged lymphocyte survival (2013)
  • Author(s): Eisaburo Sueoka, Naoko Sueoka-Aragane, Akemi Sato, Masaru Ide, Hideaki Nakamura, Yusuke Sotomaru, Choji Taya, Hiromichi Yonekawa, Tomoyuki Kitagawa, Yasushi Kubota, Shinya Kimura, Kei Nakachi, Keiji Tanimoto
  • Journal Title: PLOS ONE Volume: 8 Pages: e57833
  • Peer Reviewed
• [Journal Article] Genetic variations in detoxification enzymes and HIF-1αin Japanese patients with COPD (2013)
  • Author(s): Andika C. Putra, Keiji Tanimoto, Marina Arifin, Budhi Antariksa, Keiko Hiyama
  • Journal Title: Clinical Respiratory Journal 2013 Volume: 7 Pages: 7-15
  • Peer Reviewed
• [Journal Article] TMEM158 and FBLP1 as Novel Marker Genes of Cisplatin Sensitivity in Non-small Cell Lung Cancer Cells (2012)
  • Author(s): Ahmed El Sayed Mohammed, Hidetaka Eguchi, Satoru Wada, Nobuyuki Koyama, Michio Shimizu, Keiko Otani, Megu Ohtaki, Keiji Tanimoto, Keiko Hiyama, Mohammed Soliman Gaber, Masahiko Nishiyama
  • Journal Title: Experimental Lung Research Volume: 38 Pages: 463-74
  • Peer Reviewed
• [Journal Article] A Step forward into respiratory genetics : Overview contribution of genetics in respiratory diseases (2012)
  • Author(s): Andika C. Putra, Keiji Tanimoto, Elisna Syahruddin, Sita Andarini, Yoshio Hosoi, Keiko Hiyama
  • Journal Title: Asian Biomedicine Volume: 5 Pages: 639-651
  • Peer Reviewed
• [Journal Article] IL-1β-mediated up-regulation of DEC1 in human gingiva cells via the Akt pathway (2012)
  • Author(s): Ujjal K. Bhawal, Yumi Ito, Keiji Tanimoto, Fuyuki Sato, Katsumi Fujimoto, Takeshi Kawamoto, Tomonori Sasahira, Nobushiro Hamada, Hiroki Kuniyasu, Hirohisa Arakawa, Yukio Kato, Yoshimitsu Abiko
  • Journal Title: Journal of Cellular Biochemistry Volume: 113 Pages: 3246-3253
  • Peer Reviewed
• [Journal Article] Basic helix-loop-helix transcription factor DEC1 negatively regulates CyclinD1 (2011)
  • Author(s): Ujjal K. Bhawal, Fuyuki Sato, Yuki Arakawa, Katsumi Fujimoto, Takeshi Kawamoto, Keiji Tanimoto, Yumi Ito, Tomonori Sasahira, Takashi Sakurai, Masaru Kobayashi, Isamu Kashima, Hiroshi Kijima, Hiroki Kuniyasu, Yoshimitsu Abiko, Yukio Kato, Sadao Sato
  • Journal Title: Journal of Pathology Volume: 224 Pages: 420-429
  • Peer Reviewed
• [Journal Article] HIF-1αpolymorphisms associate with genetic aberrations in lung cancer (2011)
  • Author(s): Andika C. Putra, Keiji Tanimoto, Marina Arifin, Keiko Hiyama
  • Journal Title: Respirology Volume: 16 Pages: 796-802
  • Peer Reviewed
• [Presentation] 低酸素研究の10年−低酸素応答のゲノム研究− (2012)
  • Author(s): 谷本圭司
  • Organizer: 第10回がんとハイポキシア研究会特別企画シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2012-12-06
• [Presentation] がん細胞における低酸素応答機構の解明 (2012)
  • Author(s): 谷本圭司
  • Organizer: 島根大学医学部がんプロフェッショナル養成プランセミナー
  • Place of Presentation: 出雲
  • Year and Date: 2012-03-22
• [Presentation] DNA修復関連遺伝子の低酸素応答性転写抑制機構 (2011)
  • Author(s): 谷本圭司,中村秀明,河本健,加藤幸夫,檜山英三,檜山桂子,西山正彦,森田明典,細井義夫
  • Organizer: 第54回放射線影響学会ワークショップ低酸素バイオロジー研究に基づく放射線生物学・放射線腫瘍学の新展開
  • Place of Presentation: 神戸
  • Year and Date: 2011-11-19
• [Presentation] がん細胞における低酸素応答機構の解明 (2011)
  • Author(s): 谷本圭司
  • Organizer: 佐賀大学医学部セミナー
  • Place of Presentation: 佐賀
  • Year and Date: 2011-06-03
• [Presentation] がん細胞におけるVHL蛋白制御機構 (2011)
  • Author(s): 谷本圭司,江口英孝,和田智,西山正彦,檜山英三,中村秀明,Lorenz Poellinger,檜山桂子
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 札幌
  • Year and Date: 2011-01-30