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2002 Fiscal Year Final Research Report Summary

ANALYSIS OF THE SIGNAL TRANSDUCTION OF CELL MOTILITY INDUCED BY EGF STIMULATION IN HUMAN ORAL CANCER CELLS

Research Project

Project/Area Number 13672115
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionGIFU UNIVERSITY

Principal Investigator

SHIBATA Tohiyuki  GIFU UNIV., SCHOOL OF MED., PROFESSOR, 医学部, 教授 (50226172)

Co-Investigator(Kenkyū-buntansha) KATO Yukihiro  GIFU UNIV., SCHOOL OF MED., STAFF, 医学部, 助手 (30293567)
TOIDA Makoto  GIFU UNIV., SCHOOL OF MED., ASSOCIATE PROFESSOR, 医学部, 助教授 (90313890)
NAGAYASU Hiroki  HEALTH SCL. UNIV. OF HOKKAIDO, SCHOOL OF DENT., ASSOCIATE PROFESSOR, 歯学部, 助教授 (90265075)
YAMASHITA Tomomi  GIFU UNIV., SCHOOL OF MED., STAFF, 医学部附属病院, 助手 (80345793)
Project Period (FY) 2001 – 2002
KeywordsHUMAN / SCC / ORAL CANCER / EGF / INVASION / MATASTASIS
Research Abstract

In order to clear the effects of Epidermal Growth Factor (EGF) on the invasion abilities of human oral squamous cell carcinoma, five cell lines were studied. EGF enhanced the random motility of all cell lines in a dose-dependent fashion and exposure to EGF let to an increased production of urokinase type plasminogen activator and matrix metalloproteniase-9 by the same cells. These results strongly suggest the EGF may promote the invasion and metastasis of human oral squamous cell carcinomas. In this project, to reveal the signal pathway, we established s-1 clone cells, which was most sensitive clone against the EGF stimulation and also we established i-1 clone cells, which was most insensitive clone. Further studies were done using s-1 clone cells. When EGF bind to the EGF receptor, tyrosine phosphorelation is firstly occurred and subsequently PKC is activated through the activation of PLCr arising from erbB homodimer and/or activation of PI3-kinase arising from erbB3 heterodimer. Furthermore, erbB homodimer activates the nPKCd through the activation of PLC and also erbB/erbB-3 heterodimer activates aPKCe through the activation of PI3K. These results suggest that inhibition of aPKCe or nPKCd can reduce the invasion and metastasis of human oral cancer cells and that the useful model in the investigations of molecular target medicines is possibly established.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Hamada, J., Nakata, D,.Nakae, D., Kobayashi, Y., Akai, H., Konishi, Y., Okada, F., Shibata, T., et al.-2: "Increased oxidative DNA damage, 8-hydroxydeoxyguanosine, in rat ER-1 mammary tumor cells by continuous EGF-stimulation"J. Natl. Cancer Inst. 93. 214-219 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Nakata, J.Hamada, YiBa, K.Matsushita, T.Shibata, et al.-2: "Enhancement of tumorigenic, metastatic and in vitro invasive capacity of rat mammary tumor cells by transforming growth factor-β"Cancer Letters. 175. 95-106 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kobayashi, F.Okada, N.Fuji, N.Tomita, S.Ito, H.Tazawa, T.Aoyama, Snag Ki Choi, T.Shibata et al.-3: "Thymosin-β4 Regulates Motility and Metastasis of Malignant Mouse Fibrosarcoma Cells"American Journal of Pathology. 160. 869-875 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Hatakeyama, O.Kozawa, M.Niwa, H.Mastuno., K.Kato, N.Tatematsu, T.Shibata, et al.-1: "Inhibition by adenylyl cyclase-cAMP system of ET-1-induced HSP27 in osteoblasts"Am J Physiol Endocrenal Metab. 281. 1260-1266 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zeki Topcu, I.Chiba, M.Fujieda, T.Shibata.et al.-7: "CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka"Carcinogenesis. 23. 595-598 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Hatakeyama, O.Kozawa, T.Otsuka, T.Shibata, et al.-2: "Zinc Suppresses IL-6 Synthesis by Prostaglandin F2 α in Osteoblasts : Inhibition of Phospholipase C and Phospholipase D"J. Cellular Biochemistry. (In press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Shibata, et al.-4.: "Detection of TP53 mutation in ameloblastoma by the use of a yeast functional assay"J Oral Pathol Med 2002. 31. 534-8 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D. Hatakeyama, O. Kozawa, T. Otsuka, T. Shibata, et al.-2: "Zinc Suppresses IL-6 Synthesis by prostaglandin F2 α in Osteoblasts: Inhibition of Phospholipase C and Phospholipase D"J. Cellular Biochemistry. 9999. 1-8 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zeki Topcu, I. Chiba, M. Fujieda, T. Shibata, et al.-7: "CYP2A6 gene deletion reduces oral cancer risk tin betel quid chewers in Sri Lanka"Carcinogenesis. vol.23 (4). 595-598 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Kobayashi, F. Okuda, N. Fuji, N. Tomita, S. Ito, H, Tazawa, T. Aoyama, Sung Ki Choi, T. Shibata, et al.-3: "Thymosin-β 4 Regulates Motility and Metastasis of Malignant Monse Fibrosarcoma Cells"American J. of Pathology. 160, (3). 869-875 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D. Nakata, J. Hamada, YiBa, K. Matsushita, T. Shibata, et al.-2: "Enhancement of tumorigenic, metastatic and in vitro invasive capacity of rat mammary tumor cells by transforming growth factor-β"Cancer Letters. 175. 95-106 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D. Hatakeyama, O. Kozawa, M. Niwa, H. Mastuno, K. Kato, N. Tatematsu, T. Shibata, et al.-1: "Inhibition by adenylyl cyclase-cAMP system of ET-1-induced HSP27 in osteoblasts"Am J Physiol Enducrenal Metab. 281. 1260-1266 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamada, J., Nakata, D., Nakae, D., Kobayashi, Y., Akai, H., Konishi, Y., Okada, F., Shibata, T., et al.-2: "Increased oxidative DNA damage, 8-hydroxydeoxygnanosine, in rat ER-1 mammary tumor cells by continuous EGF-stimulation"J. Nati. Cancer Inst. 93. 214-9 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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