Cellular responses against DNA damage and search for novel molecular target

• Project/Area Number: 17016075
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: KOHNO Kimitoshi University of Occupational and Environmental Health, Japan, 医学部, 教授 (00153479)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥42,400,000 (Direct Cost: ¥42,400,000); Fiscal Year 2009: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2008: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2007: ¥8,700,000 (Direct Cost: ¥8,700,000); Fiscal Year 2006: ¥8,700,000 (Direct Cost: ¥8,700,000); Fiscal Year 2005: ¥9,000,000 (Direct Cost: ¥9,000,000)
• Keywords: DNA損傷 / 遺伝子発現制御 / YB-1 / ZNF143 / Clock / Tip60 / Wnt10A / シスプラチン / RFK / Twist / FOX03 / Ets / ペロキシレドキシン / STAT3 / HMGB1 / シグナル伝達 / 概日リズム / ATF4 / DNA

Research Abstract

Based on the analysis of drug resistant cells, we found several molecular targets such as YB-1, ZNF143, Clock and so on. These molecules are useful for cancer treatment. Molecular clocks in peripheral tissues control cell-proliferation rhythms by regulating the expression of cell-cycle genes. We also found the novel Wnt signaling pathway by which circadian disruption can induce malignant progression of tumor through angio/stromagenesis.

Research Products

• [Journal Article] Involvement of Wnt signaling in dermal fibroblasts (2010)
  • Author(s): Kabashima, K.
  • Journal Title: Am.J.Pathol. 176 Pages: 721-732
  • Peer Reviewed
• [Journal Article] Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth. (2009)
  • Author(s): Shiota, M., Izumi, H., Tanimoto, A., Takahashi, M., Miyamoto, N., Kashiwagi, E., Kidani, A., Hirano, G., Masubuchi, D., Fukunaka, Y., Yasuniwa, Y., Naito, S., Nishizawa, S., Sasaguri, Y., Kohno, K.
  • Journal Title: Cancer Res. 69(7) Pages: 3148-3156
  • Peer Reviewed
• [Journal Article] Thioredoxin2 enhances the damaged DNA binding activity of mtTFA through direct interaction (2009)
  • Author(s): Kidani, A.
  • Journal Title: Int.J.Oncol. 35 Pages: 1435-1440
  • Peer Reviewed
• [Journal Article] N-myc downstream regulated gene 1/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of inhibitor of κB kinase β expression (2009)
  • Author(s): Hosoi, F.
  • Journal Title: Cancer Res. 69 Pages: 4983-4991
  • Peer Reviewed
• [Journal Article] Nipradilol and timolol induce Foxo3a and peroxiredoxin 2 expression and protect trabecular meshwork cells from oxidative stress (2009)
  • Author(s): Miyamoto, N.
  • Journal Title: Invest.Ophthalmol.Vis.Sci. 50 Pages: 2777-2784
  • Peer Reviewed
• [Journal Article] Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth (2009)
  • Author(s): Shiota, M.
  • Journal Title: Cancer Res. 69 Pages: 3148-3156
  • Peer Reviewed
• [Journal Article] GALNT3, a gene associated with hyperphosphatemic familial tumoral calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity (2009)
  • Author(s): Chefetz, I.
  • Journal Title: Biochim.Biophys.Acta 1792 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Twist and p53 reciprocally regulate target genes via direct interaction. (2008)
  • Author(s): Shiota, M., Izumi, H., Onitsuka, T., Miyamoto, N., Kashiwagi, E., Kidani, A., Hirano, G., Takahashi, M., Naito, S., Kohno, K.
  • Journal Title: Oncogene 27(42) Pages: 5543-5553
  • Peer Reviewed
• [Journal Article] Tip60 is regulated by circadian transcription factor clock and is involved in cisplatin resistance. (2008)
  • Author(s): Miyamoto, N., Izumi, H., Noguchi, T., Nakajima, Y., Ohmiya, Y., Shiota, M., Kidani, A., Tawara, A., Kohno, K.
  • Journal Title: J. Biol. Chem. 283(26) Pages: 18218-18226
  • Peer Reviewed
• [Journal Article] Twist promotes tumor cell growth through YB-1 expression. (2008)
  • Author(s): Shiota, M., Izumi, H., Onitsuka, T., Miyamoto, N., Kashiwagi, E., Kidani, A., Yokomizo, A., Naito, S., Kohno, K.
  • Journal Title: Cancer Res. 68(1) Pages: 98-105
  • Peer Reviewed
• [Journal Article] Regulatory role of human AP-endonuclease(APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1 (2008)
  • Author(s): Chattopadhyay, R.
  • Journal Title: Mol. Cell. Biol. 28 Pages: 7066-7080
  • Peer Reviewed
• [Journal Article] Ets regulates peroxiredoxinl and 5 expressions through their interaction with the high-mobility group protein B1 (2008)
  • Author(s): Shiota, M.
  • Journal Title: Cancer Sci. 99 Pages: 1950-1959
  • Peer Reviewed
• [Journal Article] Twist and p53 reciprocally regulate target genes via direct interaction (2008)
  • Author(s): Shiota, M.
  • Journal Title: Oncogene 27 Pages: 5543-5553
  • Peer Reviewed
• [Journal Article] Tip60 is regulated by circadian transcription factor clock and is involved in cisplatin resistance (2008)
  • Author(s): Miyamoto, N.
  • Journal Title: J. Biol. Chem. 283 Pages: 18218-18226
  • Peer Reviewed
• [Journal Article] Different expression profiles of Y-box-binding protein-1 and multidrug resistance-associated proteins between alveolar and embryonal rhabdomyosarcoma (2008)
  • Author(s): Oda, Y.
  • Journal Title: Cancer Sci. 99 Pages: 726-732
  • Peer Reviewed
• [Journal Article] Expression of HER2 and estrogen receptor α depends upon nuclear locahzation of Y-box binding protein-1 in human breast cancers (2008)
  • Author(s): Fujii, T.
  • Journal Title: Cancer Res. 68 Pages: 1504-1512
  • Peer Reviewed
• [Journal Article] Transcriptional activation of STAT3 and STAT5B partially mediate HOXA1 stimulated oncogenic transformation of the immortalised human mammary epithelial cell (2008)
  • Author(s): Mohankumar, K.M.
  • Journal Title: Endocrinology
  • Peer Reviewed
• [Journal Article] Isolation and characterization of a novel H1.2 complex that acts as a repressor of p53-mediated transcription (2008)
  • Author(s): Kim, K.
  • Journal Title: J. Biol. Chem.
  • Peer Reviewed
• [Journal Article] Oncogenic Ras-induced morphologic change is through MEK/ERK signaling pathway to downregulate Stat3 at a posttranslational level in NIH3T3 cells (2008)
  • Author(s): Yeh, H.H.
  • Journal Title: Neoplasia 10 Pages: 52-60
  • Peer Reviewed
• [Journal Article] Twist promotes tumor cell growth through YB-1 expression (2008)
  • Author(s): Shiota, M.
  • Journal Title: Cancer Res. 68 Pages: 98-105
  • Peer Reviewed
• [Journal Article] ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes. (2007)
  • Author(s): Wakasugi, T., Izumi, H., Uchiumi, T., Suzuki, H., Arao, T., Nishio, K., Kohno, K.
  • Journal Title: Oncogene 26(36) Pages: 5194-5203
  • Peer Reviewed
• [Journal Article] Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines. (2007)
  • Author(s): Igarashi, T., Izumi, H., Uchiumi, T., Nishio, K., Arao, T., Tanabe, M., Uramoto, H., Sugio, K., Yasumoto, K., Sasaguri, Y., Wang, K.Y., Otsuji, Y., Kohno, K.
  • Journal Title: Oncogene 26(33) Pages: 4749-4760
  • Peer Reviewed
• [Journal Article] Stimulation of NEIL2-mediated Oxidized Base Excision Repair via YB-1 Interaction duiring Oxidative Stress (2007)
  • Author(s): Das, S.
  • Journal Title: J. Biol. Chem. 282 Pages: 28474-28484
  • Peer Reviewed
• [Journal Article] ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes (2007)
  • Author(s): Wakasugi, T.
  • Journal Title: Oncogene (in press)
• [Journal Article] Clock/ATF4 transcription system regulates drug resistance in human cancer cell lines (2007)
  • Author(s): Igarashi, T.
  • Journal Title: Oncogene (in press)
• [Journal Article] Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells (2007)
  • Author(s): Basaki, Y.
  • Journal Title: Oncogene (in press)
• [Journal Article] Impaired activity of volume-sensitive Cl^- channel is involved in cisplatin resistance of cancer cells (2007)
  • Author(s): Lee, E.L.
  • Journal Title: J. Cell. Physiol. 211・2 Pages: 513-521
• [Journal Article] Expression of GalNAc-T3 and its relationships with clinicopathological factors in 61 extrahepatic bile duct carcinomas analyzed using stepwise sections -Special reference to its association with lymph node metastases- (2007)
  • Author(s): Inoue, T.
  • Journal Title: Mod. Pathol. 20・2 Pages: 267-276
• [Journal Article] YB-1 is important for an early stage embryonic development: neural tube formation and cell proliferation. (2006)
  • Author(s): Uchiumi, T., Fotovati, A., Sasaguri, T., Shibahara, K., Shimada, T., Fukuda, T., Nakamura, T., Izumi, H., Tsuzuki, T., Kuwano, M., Kohno, K.
  • Journal Title: J. Biol. Chem. 281(52) Pages: 40440-40449
  • Peer Reviewed
• [Journal Article] YB-1 is important for an early stage embryonic development : neural tube formation and cell proliferation (2006)
  • Author(s): Uchiumi, T.
  • Journal Title: J. Biol. Chem. 281・52 Pages: 40440-40449
• [Journal Article] Fragmented hyaluronan induces transcriptional up-regulation of the multidrug resistance-1 gene in CD4+T cells (2006)
  • Author(s): Tsujimura, S.
  • Journal Title: J. Biol. Chem. 281・49 Pages: 38089-38097
• [Journal Article] Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen (2006)
  • Author(s): Kohno, Y.
  • Journal Title: Br. J. Cancer 94・5 Pages: 710-716
• [Journal Article] Expression and cellular localization of dbpC/Contrin in germ cell tumor cell lines (2006)
  • Author(s): Yoshida, T
  • Journal Title: Biochim. Biophys. Acta 1759・1-2 Pages: 80-88
• [Journal Article] Transcription factors and drug resistance. (2005)
  • Author(s): Kohno, K., Uchiumi, T., Niina, I., Wakasugi, T., Igarashi, T., Momii, Y., Yoshida, T., Matsuo, K., Miyamoto, N., Izumi, H.
  • Journal Title: Eur. J. Cancer 41(16) Pages: 2577-2586
  • Peer Reviewed
• [Journal Article] Roles of volume-sensitive Cl- channel in cisplatin-induced apoptosis in human epidermoid cancer cells. (2005)
  • Author(s): Ise, T., Shimizu, T., Lee, E.L., Inoue, H., Kohno, K., Okada, Y.
  • Journal Title: J. Membr. Biol. 205(3) Pages: 139-145
  • Peer Reviewed
• [Journal Article] Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel (2005)
  • Author(s): Fujita, T.
  • Journal Title: Clin.Cancer Res. 11・24 Pages: 8837-8844
• [Journal Article] Transcription factors and drug resistance (2005)
  • Author(s): Kohno, K.
  • Journal Title: Eur.J.Cancer 41・16 Pages: 2577-2586
• [Journal Article] Y-box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer (2005)
  • Author(s): Yoshimatsu, T.
  • Journal Title: Anticancer Res. 25・5 Pages: 3437-3443
• [Journal Article] Roles of volume-sensitive Cl-channel in cisplatin-induced apoptosis in human epidermoid cancer cells (2005)
  • Author(s): Ise, T.
  • Journal Title: J.Membr.Biol. 205・3 Pages: 139-145
• [Journal Article] Mutant IκBα suppresses hypoxia-induced VEGF expression through downregulation of HIF-1α and COX-2 in human glioma cells (2005)
  • Author(s): Kimba, Y.
  • Journal Title: Oncol.Res. 15・3 Pages: 139-149
• [Journal Article] The expression pattern of UDP-N-acetyl-α-D-galactosamine-polypeptide N-acetyl-galactosaminyl transferase-3 in squamous cell carcinoma of the esophagus (2005)
  • Author(s): Ishikawa, M.
  • Journal Title: Pathobiology 72・3 Pages: 139-145
• [Journal Article] 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induces apoptosis in colon cancer partially through the induction of Fas expression (2005)
  • Author(s): Sako, T.
  • Journal Title: In Vivo 19・1 Pages: 125-132
• [Journal Article] Significance of hypoxia in cervical cancer (2005)
  • Author(s): Kohno, K.
  • Journal Title: Int.J.Clin.Oncol. 10・1 Pages: 2-2
• [Presentation] 概日リズムに制御されるがん細胞増殖と薬剤耐性. (2009)
  • Author(s): 河野公俊, 和泉弘人
  • Organizer: 第32回日本分子生物学会年会(ワークショップ)
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] 概日リズムに制御されるがん細胞増殖と薬剤耐性 (2009)
  • Author(s): 河野公俊
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2009-12-12
• [Presentation] MCT4 expression and tumor invasion. (2009)
  • Author(s): Kohno, K.
  • Organizer: First International Symposium on Proton Transport and its Inhibition (PTI) in the etiopathogenesis, diagnosis and treatment of cancer (招待講演)
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2009-04-28
• [Presentation] MCT4 expression and tumor invasion (2009)
  • Author(s): 河野公俊
  • Organizer: First International Sympsium on Proton Transport and its Inhibition(PTI)in the etiopathogenesis, diagnosis and treatment of cancer
  • Place of Presentation: Madrid, Spain(The Ramon Areces Foundation)
  • Year and Date: 2009-04-28
• [Presentation] 抗がん剤耐性の分子機構:基礎研究から治療研究に向けて. (2008)
  • Author(s): 河野公俊
  • Organizer: 第60回日本泌尿器科学会西日本総会(招請講演)
  • Place of Presentation: 北九州
  • Year and Date: 2008-11-07
• [Presentation] Cisplatin resistance and transcription factors. (2007)
  • Author(s): Kohno, K., Izumi, H.
  • Organizer: The 12th Japanese Foundation for Cancer Research International Symposium on Cancer Chemotherapy (招待講演)
  • Place of Presentation: 東京
  • Year and Date: 2007-12-04
• [Presentation] Cisplatin resistance and transcription factors (2007)
  • Author(s): Kohno, K.
  • Organizer: The 12th Japanese Foundation for Cancer Research International Symposium on Cancer Chemotherapy
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2007-12-04
• [Presentation] 転写因子と抗がん剤耐性. (2007)
  • Author(s): 河野公俊
  • Organizer: 第16回泌尿器科分子・細胞研究会(特別講演)
  • Place of Presentation: 福岡
  • Year and Date: 2007-02-24
• [Presentation] 抗がん剤耐性の分子生物学からのアプローチ. (2006)
  • Author(s): 河野公俊
  • Organizer: 第24回日本口腔腫瘍学会総会・学術大会(特別講演)
  • Place of Presentation: 福岡
  • Year and Date: 2006-01-27
• [Presentation] Transcription factors and cisplatin resistance. (2005)
  • Author(s): Kohno, K
  • Organizer: The Japan Society for Promotion of Science (JSPS) U.S. -Japan Cooperative Cancer Research Program Seminar (招待講演)
  • Place of Presentation: 大阪
  • Year and Date: 2005-06-11
• [Book] がん化学療法・分子標的治療update (2009)
  • Author(s): 河野公俊, 和泉弘人
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.uoeh-u.ac.jp/kouza/bunsei/intro_j.html
• [Patent(Industrial Property Rights)] 胚細胞腫瘍の検出方法 (2009)
  • Inventor(s): 河野公俊, 笹栗靖之
  • Industrial Property Rights Holder: 株式会社キューリン
  • Acquisition Date: 2009-10-23
• [Patent(Industrial Property Rights)] 予後判定方法 (2009)
  • Inventor(s): 松尾憲一, 山田雄次, 河野公俊
  • Industrial Property Rights Holder: 大鵬薬品工業株式会社
  • Acquisition Date: 2009-01-30
• [Patent(Industrial Property Rights)] 胚細胞腫瘍の検出方法 (2009)
  • Inventor(s): 河野公俊, 笹栗靖之
  • Industrial Property Rights Holder: 株式会社キューリン
  • Acquisition Date: 2009-10-23
• [Patent(Industrial Property Rights)] 癌細胞増殖阻害方法、増殖阻害剤及びスクリーニング方法 (2008)
  • Inventor(s): 河野公俊, 和泉弘人, 笹栗靖之
  • Industrial Property Rights Holder: 産業医科大学
  • Filing Date: 2008-12-26
• [Patent(Industrial Property Rights)] 癌細胞増殖阻害方法、増殖阻害剤及びスクリーニング方法 (2008)
  • Inventor(s): 河野公俊, 和泉弘人, 笹栗靖之
  • Industrial Property Rights Holder: 産業医科大学
  • Filing Date: 2008-12-26
  • Overseas
• [Patent(Industrial Property Rights)] ZNF 143 GENE (2006)
  • Inventor(s): 河野公俊他
  • Industrial Property Rights Holder: 北九州TLO
  • Filing Date: 2006-12-08