Analysis of DNAdamage checkpoint regulator gene and cancer control mechanism in oral cancer

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Showa University
• Principal Investigator: KOHNO Yohko Showa University, School of Dentistry, Associate Professor (40195681)
• Co-Investigator(Kenkyū-buntansha): TAKIMOTO Masafumi Showa University, School of Medicine, Associate Professor (40179586) ; MURANIATSU Takashi Tokyo Dental College, Dept. of Pathology, Assistant Professor (00276982)
• Project Period (FY): 2005 – 2007
• Keywords: Oral cancer / DNA damage / p53 / Tumor suppressor gene

Research Abstract

Damage and abnormality of DNA genome is the starting point of the process of malignant transformation of a normal cell. Once DNA damage occurs, eukaryotic cells can activate cell cycle checkpoints, apoptosis or senescence. Some kinases are related to cell cycle checkpoint, apoptosis and senescence pathways, and stimulate and activate other kinases. p53, a transcriptional factor mutated in over 50% of human cancers, is phosphorylated at Ser15 and Ser37 by ATM/ATR and DNA-PK. This phosphorylation promotes the accumulation and functional activation of p53 in response to DNA damage. Active Chk1 and Chk2 can phosphorylate p53 at several serine : sites, enhancing its tetramerization, stability and activity. In 60% of oral cancer, p53 is mutated. It seems that some kinds of oral cancer have different signal transmission pathways which are regarded as conventional DNA damage signal transmission pathways. We used several kinds of oral squamous carcinoma cell lines to check the expression of p53 first. After treatment with genotoxic stress to culture cells, we examined the expression of each protein in DNA damage checkpoint by Western blot analysis, and checked the localization in oral mucosal tissues by immunohistochemistry.

Research Products

• [Journal Article] Heat stress induces ALP activity and HSP25 expression in cultured dental pulp (2008)
  • Author(s): Lee, MK, Muramatsu, T, Uekusa, T, Lee, JH, Shimono, M
  • Journal Title: Int Endod J 41(2) Pages: 158-62
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of connexin43 in cultured dental pulp by antisense oligonucle otides (2007)
  • Author(s): Chung CK.
  • Journal Title: Cell&Tissue Research 329 Pages: 295-300
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue (2007)
  • Author(s): Matsuzaki H.
  • Journal Title: J Oral Pathol Med. 36 Pages: 30-34
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of connexin43 in cultured dental pulp by antisense oligonucleotides (2007)
  • Author(s): Chung, CK, Muramatsu, T, Uekusa, T, Sasaki, H, Shimono, M
  • Journal Title: Cell & Tissue Research 329(2) Pages: 295-300
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue (2007)
  • Author(s): Matsuzaki, H, Shima, K, _Muramatsu, T, Ro, Y, Hashimoto, S, Shibahara, T, Shimono, M
  • Journal Title: J Oral Pathol Med 36(1) Pages: 30-4
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hypermethylation of CpG islands in p16 as a prognostic factor for diffuse large B-cell lymphoma in a high-risk group (2006)
  • Author(s): Shiozawa, E, Takimoto, M, . Makino, R, Adachi, D, Saito, B, Yamochi-Onizuka, T, Shimozuma, J, Maeda, T, Kohno, Y, Kawakami, K, Nakamaki, T, Tomoyasu, S, Shiokawa, A, Ota, H
  • Journal Title: Leuk Res
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Connexin 43 transfection in basaloid squamous cell carcinoma cells (2006)
  • Author(s): Shima, K, Muramatsu, T, Abiko, Y, Yamaoka, Y, Sasaki, H, Shimono, M
  • Journal Title: Oncol Rep 16(2) Pages: 285-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Correlation between reduction, of syndecan-1 expression and clinico-pathological parameters in squamous cell carcinoma of tongue (2006)
  • Author(s): Ro, Y, Muramatsu, T, Shima, K, Yajima, Y, Shibahara, T, Noma, H, Shimono, M
  • Journal Title: Int J Oral Maxillofac Surg 35(3) Pages: 252-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Microarray Analysis on Odontogenesis-related -genes in Mouse Dental Papillae (2005)
  • Author(s): Muramatsu, T, Sasaki, H, Yamamoto, H, Kohno, Y, Cho, SW, Jung, FS, Shimono, M
  • Journal Title: J Hard Tissue Biol 14(2) Pages: 180-182
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of osteopontin expression and function in oral cancer cell lines by antisense oligonucleotides (2005)
  • Author(s): Muramatsu, T, Shima, K, Ohta, K, Kizaki, H, Ro, Y, Kohno, Y, Abiko, Y, Shimono, M
  • Journal Title: Cancer Lett 217(1) Pages: 87-95
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] p53 phosphorylation in mouse skin and in vitro human skin model by high-dose-radiation exposure (2005)
  • Author(s): Koike, M, Sugasawa, J, Koike, A, Kohno, Y
  • Journal Title: J Radiat Res(Tokyo) 46(4) Pages: 461-468
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo (2005)
  • Author(s): Kim-Kanayama, J., Suzuki, W., lehikawa., K., Ohki., T., Kohno., Y., Sata., M., Nose., K., S., hibanuma., M., Uni-axial
  • Journal Title: J Cell Sci 118 Pages: 937-949
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of osteopontin expression and function in oral cancer cell lines by antisense oligonucleotides (2005)
  • Author(s): Muramatsu, T., Shima, K., Ohta, K., Kizaki, H., Ro, Y., Kohno, Y., Abiko, Y., Shimono, M
  • Journal Title: Cancer letters 217 Pages: 87-95
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of laminin and integrins in adhesion and migration of junctiona epithelium cells
  • Author(s): Kunimatsu T.
  • Journal Title: J Periodontal Res
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Involvement of laminin and integrins in adhesision and migration of junctional epithelium cells
  • Author(s): Kinumatsu, T, Hashimoto, S, Muramatsu, T, Sasaki, H, Jung, HS, Yamada, S, Shimono, M
  • Journal Title: J Periodontal Res (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Protein expression of DNA damage checkpoint control pathway in oral cancer (2007)
  • Author(s): Kohno, Y, Takimoto, M, Shiozawa, E, Ota, H
  • Organizer: Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 20071003-05
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Analysis of protein expression of DNA damage checkpoint pathway in oral cancer (2007)
  • Author(s): Kohno, Y, Takimoto, M, Shiozawa, E, Ota, H
  • Organizer: Annual Meeting of the Japanese society of Pathology
  • Place of Presentation: Osaka
  • Year and Date: 20070313-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 虚空癌のDNA損傷におけるチェックポイント制御機構での各タンパク発現について (2007)
  • Author(s): 河野 葉子
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-04
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Analysis of DNA damage checkpoint pathway in oral cancer (2006)
  • Author(s): Kohno, Y, Takimoto, M, Shiozawa, E, Ota, H
  • Organizer: Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 20060928-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] It is not necessary that p53 and H2AX phosphorylation in mouse skin and In Vitro Human skin model by High-Dose-Radiation exposure (2006)
  • Author(s): Sugasawa, J, Kohno, Y, Koike, M
  • Organizer: Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 20060928-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] p53 Phosphorylation In Mouse Skin. And In Vitro Human Skin Model By High-Dose-Radiation Exposure (2006)
  • Author(s): Kohno, Y., Sugasawa, J., Koike, A., Koike, M
  • Organizer: 7th Joint Meeting of The Histochemical Society & The Japan Society of Histo-chemistry and Cytochemistry
  • Place of Presentation: Hawaii, USA
  • Year and Date: 20060800
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Gluconolactonase activity and deficiency of Senescence Suppressor protein(SMP30) (2006)
  • Author(s): Maruyama, N, Ishigami, A, Handa, S, Kohno, Y
  • Organizer: Annual Meeting of the Japanese society of Pathology
  • Place of Presentation: Tokyo
  • Year and Date: 20060430-0502
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The expression of syndecan-1 in human oral cancer cell line (2005)
  • Author(s): Ro, Y, Shibahara, T, Muramatsu, T, Shima, K, Shimono, M, Ohta, K, Yajima, Y
  • Organizer: Cngress of Maxillofacial surgery
  • Place of Presentation: Daemyung Vivaldi park Resort, Korea
  • Year and Date: 20050421-23
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Expression of osteopontin in oral squamous cell carcinoma. Oral Oncology Vol.1 No.1 Page157 (2005)
  • Author(s): Shima, K, Muramatsu, T, Ro, Y, Sazuka, A, Shimono
  • Organizer: The 10th International Congress of Oral Cancer
  • Place of Presentation: Islands of Creta, Greece
  • Year and Date: 20050419-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Function of syndecan-1 in human oral cancer cell Line (2005)
  • Author(s): Muramatsu, T, Shima, K, Kohno, Y, Abiko, Y, Hashimoto, M, Shimono, M
  • Organizer: Annual Meeting of the Japanese society of Pathology
  • Place of Presentation: Yokohama
  • Year and Date: 20050414-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Gene expression of tooth bud and pulp by GeneChip microarray (2005)
  • Author(s): Sasaki, H, Muramatsu, T, Ohta, K, Kimizuka, R, Hashimoto, M., Shimono, M
  • Organizer: Annual meeting of Tokyo dental collage
  • Place of Presentation: Chiba
  • Year and Date: 2005-06-04
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Expression of laminin-5, integrin-beta4 and syndecan-1 in various type of ameloblastoma The Korean Journal of Oral and Maxillofacial Pathology 29(2) : 167, 2005 (0)
  • Author(s): Sasaki, H, Shima, K, Matsuki, M, Enokiya, Y, Muramatsu, T, Inoue, T, Hashimoto, S, Shimono, M
  • Organizer: Cogress of Asian Oral and maxillofacial society of Pathology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 00000527
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] A case of clear cell variant of mucoepidermoid carcinoma with oncocytic metaplasia The Korean Journal of Oral and Maxillofacial Pathology 29(2) : 167, 2005 (0)
  • Author(s): Muramatsu, T, H., ashimono, S, Inoue, T, Ogawa, I, Takata, T, Shimono, M
  • Organizer: Cogress of Asian Oral and maxillofacial society of Pathology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 00000527
  • Description: 「研究成果報告書概要(欧文)」より