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Hypoxia-responsive MYC promotes the survival and growth of pleomorphic adenoma cells in hypoxic conditions.

Research Project

Project/Area Number 15K11069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNiigata University

Principal Investigator

Maruyama Satoshi  新潟大学, 医歯学総合病院, 講師 (30397161)

Co-Investigator(Kenkyū-buntansha) 阿部 達也  新潟大学, 医歯学総合研究科, 特任助教 (70634856)
山崎 学  新潟大学, 医歯学系, 助教 (10547516)
程 クン  新潟大学, 医歯学系, 准教授 (40207460)
朔 敬  大阪歯科大学, 歯学部, 客員教授 (40145264)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords唾液腺多形性腺腫 / 低酸素 / HIF-1α / c-Myc / SM-AP
Outline of Final Research Achievements

On the basis of hypovasucularity of the salivary pleomorphic adenoma, we had a hypothesis that pleomorphic adenoma cells are able to survive in hypoxic conditions. To understand the hypoxia-dependent manner of energy metabolism in this particular tumor, we analyzed function of MYC, which are the most important factor of metabolic regulation, in cell proliferation and migration in hypoxic-conditioned pleomorphic adenoma cells. In hypoxic condition, SM-AP cells, human pleomorphic adenoma cell systems, showed higher gene expression levels of HIF-1α and MYC in hypoxia. HIF-1α protein was also kept in higher levels and localized more significantly in nuclei. The proliferation and migration of SM-AP cells were reduced under the lack of MYC expression. These results indicated that hypoxic conditions induced pleomorphic adenoma cells to produce MYC, which was maintained by high HIF-1α protein levels.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] A case of small cell carcinoma arising in the palatine gland2017

    • Author(s)
      Kojima T, Mikami T, Hayashi T, Maruyama S, Yamazaki M, Kobayashi T.
    • Journal Title

      Jpn. J. Oral Maxillofac Surg.

      Volume: 67(7) Pages: 358-363

    • NAID

      130006083396

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 上顎に発生した唾液腺導管癌の1例2017

    • Author(s)
      堀野 一人, 小林 孝憲, 飯田 明彦, 斎藤 太郎, 大西 眞, 丸山 智
    • Journal Title

      新潟歯学会雑誌

      Volume: 47(1) Pages: 39-43

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic and histopathological characterization of the interface between oral squamous cell carcinoma invasion fronts and non-cancerous epithelia2017

    • Author(s)
      Abe T, Maruyama S, Yamazaki M, Xu B, Babkair H, Sumita Y, Cheng J, Yamamoto T, Saku T
    • Journal Title

      Experimental and Molecular Pathology

      Volume: 102 Issue: 2 Pages: 327-336

    • DOI

      10.1016/j.yexmp.2017.02.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression of neprilysin in periodontitis-affected gingival tissues.2017

    • Author(s)
      Nezu A, Kubota T, Maruyama S, Nagata M, Nohno K, Morizumi T, Yoshie H.
    • Journal Title

      Arch Oral Biol.

      Volume: 79 Pages: 35-41

    • DOI

      10.1016/j.archoralbio.2017.03.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumor-associated macrophages are recruited and differentiated in the neoplastic stroma of oral squamous cell carcinoma.2016

    • Author(s)
      Essa AAM, Yamazaki M, Maruyama S, Abe T, Babkair H, Raghib AM, Megahed EMED, Cheng J, Saku T.
    • Journal Title

      Pathology

      Volume: 48(3) Issue: 3 Pages: 219-227

    • DOI

      10.1016/j.pathol.2016.02.006

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma2016

    • Author(s)
      Babkair H, Yamazaki M, Uddin MS, Maruyama S, Abe T, Essa A, Sumita Y, Ahsan MS, Swelam W, Cheng J, Saku T
    • Journal Title

      Human Pathology

      Volume: 57 Pages: 51-60

    • DOI

      10.1016/j.humpath.2016.07.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Clinical significance of intraoral strain elastography for diagnosing early stage tongue carcinoma: a preliminary study.2016

    • Author(s)
      Shingaki M, Nikkuni Y, Katsura K, Ikeda N, Maruyama S, Takagi R, Hasashi T.
    • Journal Title

      Oral Radiol.

      Volume: 32 Issue: 3 Pages: 1-8

    • DOI

      10.1007/s11282-016-0269-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.2016

    • Author(s)
      Hasegawa M, Cheng J, Maruyama S, Yamazaki M, Abe T, Babkair H, Saito C, Saku T.
    • Journal Title

      Pathol Res Pract.

      Volume: 212(5) Issue: 5 Pages: 426-436

    • DOI

      10.1016/j.prp.2016.02.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protease-activated receptor-2 modulates proliferation and invasion of oral squamous cell carcinoma cells.2015

    • Author(s)
      Al-Eryani K, Cheng J, Abe T, Maruyama S, Yamazaki M, Babkair H, Essa A, Saku T
    • Journal Title

      Human Pathology

      Volume: in press Issue: 7 Pages: 991-999

    • DOI

      10.1016/j.humpath.2015.03.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paradental cyst is an inclusion cyst of the junctional/sulcular epithelium of the gingiva: histopathologic and immunohistochemical confirmation for its pathogenesis.2015

    • Author(s)
      Maruyama S, Yamazaki M, Abe T, Babkair H, Cheng J, Saku T.
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol.

      Volume: 120(2) Issue: 2 Pages: 227-237

    • DOI

      10.1016/j.oooo.2015.04.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simultaneous immunolocalization of desmoglein 3 and IgG4 in oral pemphigus vulgaris: IgG4 predominant autoantibodies in its pathogenesis.2014

    • Author(s)
      Abe T, Maruyama S, Babkair H, Yamazaki M, Cheng J, Saku T
    • Journal Title

      Journal of Oral Pathology and Medicine

      Volume: 該当なし Issue: 10 Pages: 850-856

    • DOI

      10.1111/jop.12290

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 免疫組織化学の導入による口腔上皮性異形成・上皮内癌の客観的病理組織診断の均霑化をめざして2018

    • Author(s)
      丸山 智, 阿部達也, 山崎 学
    • Organizer
      第36回日本口腔腫瘍学会総会・学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 低酸素環境下でMYCは唾液腺多形性腺腫由来細胞の生存・増殖を亢進する.2017

    • Author(s)
      丸山 智, 山﨑 学, 阿部達也, 隅田賢正, 程 クン, 朔  敬
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MYCは低酸素環境下における唾液腺多形性腺腫由来細胞の生存・増殖を亢進する2017

    • Author(s)
      丸山 智, 山﨑 学, 阿部達也, 隅田賢正, 程 クン, 朔  敬
    • Organizer
      第28回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 分科会プログラム「口腔粘膜早期癌の診断」口腔癌早期病変の客観的病理組織診断:免疫組織化学をもちいた診断の均霑化をめざして2016

    • Author(s)
      丸山 智
    • Organizer
      第23回日本歯科医学会総会
    • Place of Presentation
      福岡国際会議場 福岡サンパレス(福岡県 福岡市)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔表在性病変におけるP53免疫組織化学的検索の取り組み2016

    • Author(s)
      丸山 智, 山﨑 学, 阿部達也, バブカイール ハムザ, 隅田賢正, 程 クン
    • Organizer
      第27回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      広島大学 応仁会館(広島県 広島市)
    • Year and Date
      2016-08-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 唾液腺多形腺腫細胞は低酸素環境下でHF-1αーMYC相互作用によってエネルギー代謝を制御している2016

    • Author(s)
      丸山 智, 山﨑 学, 阿部達也, バブカイール ハムザ, 隅田賢正, 程 クン, 朔  敬
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県 仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Presentation] Why is it pleomorphic? Reasons for colorful but hypoxic stroma of pleomorphic adenoma of the salivary gland.2015

    • Author(s)
      Maruyama S
    • Organizer
      The 7rd Meeting of Asian Societry of Oral and Maxillofacial Pathology.
    • Place of Presentation
      Taipei (Taiwan )
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] YAP modulates proliferation-differentiation phase switching in oral squamous cell carcinoma and its differentiatin represents skin-type orthokeratotsis.2015

    • Author(s)
      Abe T, Maruyama S, Yamazaki M, Babkair H, Sumita Y, Cheng J, Saku T.
    • Organizer
      The 7rd Meeting of Asian Societry of Oral and Maxillofacial Pathology.
    • Place of Presentation
      Taipei(Taiwan)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新潟大学医歯学総合病院での病理診断における免疫組織化学的検索の取り組み.2015

    • Author(s)
      丸山 智, 山崎 学, 阿部達也, ハムザ バブカイル, 隅田賢正, 程 クン, 朔  敬
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      北海道大学・学術交流会館(北海道・札幌市)
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
  • [Presentation] YAPは口腔扁平上皮癌の増殖ー分化の分岐スイッチの役目を担っている:正角化関連分子の動態解析から.2015

    • Author(s)
      阿部達也, 丸山 智, 山崎 学, Babkair H, 隅田賢正, 程 クン, 朔  敬
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      北海道大学・学術交流会館(北海道・札幌市)
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 低酸素応答ファイブロネクチン生合成が唾液腺多形性腺腫由来SM-AP細胞の増殖を促進する.2015

    • Author(s)
      丸山 智, 山崎 学, 阿部達也, バブカイル ハムザ, 程 クン, 朔  敬
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Presentation] 口腔扁平上皮癌および正角化型異型上皮における正角化関連分子の動態.2015

    • Author(s)
      阿部達也, 丸山 智, 山崎 学, バブカイル ハムザ, 程 クン, 朔  敬
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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