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A study on the senescence-inducing therapy to oral cancer by targeting IκB kinase

Research Project

Project/Area Number 13672104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKumamoto University (2002)
Kyushu University (2001)

Principal Investigator

IKEBE Tetsuro  Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (20202913)

Co-Investigator(Kenkyū-buntansha) 白砂 兼光  九州大学, 歯学研究院, 教授 (30093420)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsoral cancer / IKK / NF-κB / epithelial differentiation / involucrin / squamous cell carcinoma / NF-κB
Research Abstract

We investigated the function of IκB kinase (IKK) α in oral squamous cell carcinoma (SCC).
(1) At first, we examined the expressions of IKK as well as NF-κB in oral SCC tissues. IKK α is a kinase to activate NF-κB, and NF-κB is a transcription factor to transactivate anti-apoptotic genes. Thirty six biopsy specimens from patients with SCC were immunohistochemically stained. The results show that high expressions of IKKα and NF-κB p65 correlated with the invasiveness and the nodal involvement of oral SCC.
(2) We caused cultured oral SCC cell line to overexpress IKKα or IKKβ by transfecting its expression vector. High levels of IKKα, but not IKKβ, inhibited the expressions of epithelial differentiation markers, involucrin and filaggrin, in SCC cells. Phorbol myristate acetate phosphorylated IKKα to inhibit the expressions of involucrin. Protein kinase C and IKKα may regulate the differentiation and senescence of SCC cells.
The results described above suggest that high expressions of IKKα may contribute to the tumor survival by inhibiting the differentiation (and senescence) in SCC cells. Therefore, IKKα seems to be a therapeutic target molecule against oral cancer.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] H.Nakayama, T.Ikebe, M.Beppu, K.Shirasuna: "High Expression Lavels of Nuclear Factor kB, IkB Kinase a and Akt Kinase in Squamous Cell Carcinoma of the Oral Cavity"Cancer. 92. 3037-3044 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideki Nakayama, Tetsuro Ikebe, Kanemitsu Shirasuna: "High expression levels of nuclear factor κB, IκB kinase α and Akt kinase in squamous cell carcinoma of the oral cavity"Cancer. 92. 3037-3044 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Nakayama, T.Ikebe, M.Beppu, K.Shirasuna: "High Expression Lavels of Nuclear Factor kB, IkB Kinase a and Akt Kinase in Squamous Cell Carcinoma of the Oral Cavity"Cancer. 92. 3037-3044 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Beppu, T.Ikebe, K.Shirasuna: "The inhibitory Effects of immunosuppressive factors, dexamethasone and interleukin-4, on NF-kB-mediated protease production by oral cancer"Biochimica et Biophysica Acta. 1586. 11-22 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] F.Sandra, N.Matsuki, H.Takeuchi, T.Ikebe et al.: "TNF inhibited the apoptosis by activation of Akt serine/threonine kinase in the human head and neck squamous cell carcinoma"Cellular Signalling. 14. 771-778 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakayama, H., Ikebe, T., Beppu, M., Shirasuna, K.: "High expression levels of nuclear factor κB, 1κB kinase a and Akt kinase in squamous cell carcinoma of the oral cavity"Cancer. 92. 3037-3044 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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