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Pathophysiological significance of altered kerakin expression in oral cancer

Research Project

Project/Area Number 21592320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SAKAMOTO Kei  東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (00302886)

Co-Investigator(Renkei-kenkyūsha) YAMAGUCHI Akira  東京医科歯科大学, 医歯学総合研究科, 教授 (00142430)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords口腔病理学 / 口腔癌 / 前癌病変 / Notch / ケラチン / 扁平上皮癌 / 上皮異形成 / Notch1
Research Abstract

We clarified basal-cell dominant expression of NOTCH1 in squamous epithelium. NOTCH1 was downregulated in squamous neoplasms of oral mucosa, esophagus and uterine cervix, compared to the normal basal cells, although the expression tended to be retained in cervical lesions. NOTCH1 downregulation was observed even in precancers, and there was little difference between cancers and high-grade precancerous lesions, suggesting its minor contribution to cancer-specific events such as invasion. In culture experiments, reduction of NOTCH1 expression resulted in downregulation of keratin 13 and keratin 15, and upregulation of keratin 17, and NOTCH1 knockdown cells formed a dysplastic stratified epithelium mimicking a precancerous lesion. The NOTCH1 downregulation and the concomitant alterations of those keratin expressions were confirmed in the squamous neoplasms both by immunohistochemical and cDNA microarray analyses. Our data indicate that reduction of NOTCH1 expression directs the basal cells to cease terminal differentiation and to form an immature epithelium, thereby playing a major role in the histopathogenesis of epithelial dysplasia. Furthermore, downregulation of NOTCH1 expression seems to be an inherent mechanism for switching the epithelium from a normal and mature state to an activated and immature state, suggesting its essential role in maintaining the epithelial integrity.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (17 results)

All 2012 2011 2010 2009

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (12 results)

  • [Journal Article] Reduction of NOTCH1 expression pertains tomaturation abnormalities of keratinocytesin squamous neoplasms2012

    • Author(s)
      Sakamoto K, Fujii T, Kawachi H, Miki Y, Omura K, Morita KI, Kayamori K, Katsube KI, Yamaguchi A
    • Journal Title

      Lab Invest

      Volume: 92(5) Pages: 688-702

    • Related Report
      2011 Final Research Report
  • [Journal Article] Reduction of NOTCH1 expression pertains to maturation abnormalities of keratinocytes in squamous neoplasms2012

    • Author(s)
      Sakamoto K, Fujii T, Kawachi H, Miki Y, Omura K, Morita KI, Kayamori K, Katsube KI, Yamaguchi A
    • Journal Title

      Laboratory investigation

      Volume: (Epub ahead of print) Issue: 5 Pages: 688-702

    • DOI

      10.1038/labinvest.2012.9

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of NOTCH1 expression pertains to maturation abnormalities of keratinocytes in squamous neoplasms2011

    • Author(s)
      Sakamoto K, Aragaki T, Kawachi H, Katsube K, Miki Y, Takizawa T, Omura K, Morita K, Okada N, Yamaguchi A
    • Journal Title

      Lob Invest

      Volume: 92 Issue: 4 Pages: 688-702

    • DOI

      10.1111/j.1365-2559.2011.03759.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive keratin profiling revealsdifferent histopathogenesis ofkeratocystic odontogenic tumor and orthokeratinized odontogenic cyst2010

    • Author(s)
      Aragaki T, Michi Y, Katsube K, Uzawa N, Okada N, Akashi T, Amagasa T, Yamaguchi A, Sakamoto K.
    • Journal Title

      Hum Pathol

      Volume: 41(12) Pages: 1718-25

    • Related Report
      2011 Final Research Report
  • [Journal Article] Comprehensive keratin profiling reveals different histopathogenesis ofkeratocystic odontogenic tumor and orthokeratinized odontogenic cyst.2010

    • Author(s)
      Aragaki T, Michi Y, Katsube K, Uzawa N, Okada N, Akashi T, Amagasa T, Yamaguchi A, Sakamoto K
    • Journal Title

      Human Pathology

      Volume: 41(12) Pages: 1718-1725

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] エナメル上皮腫の病理診断2012

    • Author(s)
      坂本啓、山口朗
    • Organizer
      第30回日本口腔腫瘍学会総会・学術大会ワークショップ4
    • Place of Presentation
      大宮
    • Year and Date
      2012-01-27
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional role of Keratin 17 in oralcancer2012

    • Author(s)
      カノムルマナ、坂本啓、山口朗
    • Place of Presentation
      大宮
    • Related Report
      2011 Final Research Report
  • [Presentation] 顎骨内の嚢胞及び嚢胞性病変のケラチン発現に関する検討2012

    • Author(s)
      新垣理宣、坂本啓、道泰之、鈴木まどか、山城正司、倉林亨、山口朗
    • Place of Presentation
      大宮
    • Related Report
      2011 Final Research Report
  • [Presentation] 口腔扁平上皮癌による骨破壊には腫瘍細胞と間質細胞が産生するRANKLが関与する2012

    • Author(s)
      佐藤潔、坂本啓、栢森高、小村健、山口朗
    • Place of Presentation
      大宮
    • Related Report
      2011 Final Research Report
  • [Presentation] NOTCH1の口腔癌の病態における意義2011

    • Author(s)
      坂本啓、山口朗
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-29
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Keratin expression in oral squamous cell carcinomaand epithelial dysplasia2010

    • Author(s)
      Kei Sakamoto, Akira Yamaguchi
    • Organizer
      15th International Congress of Oral Pathologyand Medicine
    • Place of Presentation
      Seoul、Korea
    • Year and Date
      2010-08-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Keratin expression in oral squamous cell carcinoma and epithelial dysplasia2010

    • Author(s)
      Kei Sakamoto, Akira Yamaguchi
    • Organizer
      15th International Congress of Oral Pathology and Medicine
    • Place of Presentation
      ソウル、韓国
    • Year and Date
      2010-08-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 角化嚢胞性歯原性腫瘍と正角化歯原性嚢胞におけるケラチン発現とその病態発生における役割2010

    • Author(s)
      新垣理宣、坂本啓、勝部憲一、天笠光雄、山口朗
    • Organizer
      第21回日本臨床口腔病理学会学術大会
    • Place of Presentation
      大阪歯科大学葛葉学舎、大阪
    • Year and Date
      2010-08-01
    • Related Report
      2011 Final Research Report
  • [Presentation] 口腔扁平上皮癌・上皮異形成におけるケラチン発現の網羅的解析2010

    • Author(s)
      大阪歯科大学葛葉学舎、大阪坂本啓、森田圭一、小村健、山口朗
    • Organizer
      第21回日本臨床口腔病理学会学術大会
    • Place of Presentation
      大阪歯科大学葛葉学舎、大阪
    • Year and Date
      2010-08-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Notch1は口腔粘膜の上皮異形成と扁平上皮癌で発現が減弱している2009

    • Author(s)
      坂本啓、勝部憲一、岡田憲彦、山口朗
    • Organizer
      第20回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      札幌
    • Year and Date
      2009-07-31
    • Related Report
      2011 Final Research Report
  • [Presentation] Notch 1は口腔粘膜の上皮異形成と扁平上皮癌で発現が減弱している2009

    • Author(s)
      坂本啓、勝部憲一、岡田憲彦、山口朗
    • Organizer
      第20回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      札幌
    • Year and Date
      2009-07-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] 口腔上皮異形成・扁平上皮癌のバイオマーカーとなるケラチン4の発現調節機構の解明の試み2009

    • Author(s)
      坂本啓、山口朗
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-03
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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