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Molecular pathological analyses of proneural/neuroendocrine phenotype-obtaining mechanisms on lung cancer cells

Research Project

Project/Area Number 24590428
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionChiba University (2014)
Kyorin University (2012-2013)

Principal Investigator

YAZAWA Takuya  千葉大学, 医学(系)研究科(研究院), 准教授 (50251054)

Co-Investigator(Kenkyū-buntansha) SATO Hanako  聖マリアンナ医科大学, 医学部, 助教 (60438132)
HARA Yukiko  杏林大学, 医学部, 講師 (40313267)
SHIMOYAMADA Hiroaki  杏林大学, 医学部, 講師 (60381472)
FUJIWARA Masachika  杏林大学, 医学部, 講師 (20407026)
KAMMA Hiroshi  杏林大学, 医学部, 教授 (10195191)
Research Collaborator ISHII Jun  
SAKAEDA Masashi  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords肺癌 / 神経内分泌癌 / 小細胞肺癌 / 大細胞神経内分泌癌 / カルチノイド腫瘍 / 分化形質 / 転写因子 / POU / 人体病理学 / 分子病理学 / 小細胞癌
Outline of Final Research Achievements

One-third of lung malignancies demonstrate a proneural/neuroendocrine phenotype, and lung cancers having a proneural/neuroendocrine phenotype reveal poor prognosis. However, it has not been elucidated how a proneural/neuroendocrine differentiation is controlled in lung cancers. Therefore, we conducted molecular pathological analyses of proneural/neuroendocrine phenotype-obtaining mechanisms on lung cancer cells, focusing upon homeobox gene expression. Small cell lung cancer cells specifically expressed LHX2, LHX6, and class III/IV POU transcription factors. Among them, class III/IV POU transcription factors could induce proneural and neuroendocrine marker genes, and especially, POU3F4 and POU4F2 could effectively be transformed large cell carcinoma cells into neuroendocrine cancer cells. These findings suggested that POU3F4 and POU4F2 play crucial roles on obtaining proneural-neuroendocrine phenotype in lung cancers.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (23 results)

All 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (14 results) (of which Invited: 3 results)

  • [Journal Article] Expression of developing neural transcription factors in lung carcinoid tumors2014

    • Author(s)
      Endo T, Yazawa T, Shishido-Hara Y, FUjiwara M, Shimoyamada H, Ishii J, Sato H, Tachibana K, Takei H, Kondo H, Goya T, Endo S, Kamma H
    • Journal Title

      Pathology International

      Volume: 64 Issue: 8 Pages: 365-374

    • DOI

      10.1111/pin.12183

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Class III/IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation2014

    • Author(s)
      Ishii J, Sato H, Yazawa T, Shishido-Hara Y, Hiramatsu C, Nakatani Y, Kamma H
    • Journal Title

      Pathology International

      Volume: 64 Issue: 9 Pages: 415-422

    • DOI

      10.1111/pin.12198

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] C viral inclusions in progressive multifocal leukoencephalopathy: Scaffolding promyelocytic leukemia nuclear bodies grow with cell cycle transition through an S-to-G2-like state in enlarging oligodendrocyte nuclei2014

    • Author(s)
      Shishido-Hara Y, Yazawa T, Nagane M, Higuchi K, Abe-Suzuki S, Kurata M, Kitagawa M, Kamma H, Uchihara T
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 73 Issue: 5 Pages: 442-453

    • DOI

      10.1097/nen.0000000000000066

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CT analysis of the effect of pirfenifone in patients with idiopathic pulmonary fibrosis.2014

    • Author(s)
      Iwasawa T, Ogura T, Sakai F, Kanauchi T, Komagata T, Baba T, Gotoh T, Morita S, Yazawa T, Inoue T.
    • Journal Title

      Eur J Radiol

      Volume: 83 Issue: 1 Pages: 32-38

    • DOI

      10.1016/j.ejrad.2012.02.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prenatal diagnosis of umbilical artery thrombosis.2014

    • Author(s)
      Tanaka K, Tanigaki S, Matsushima M, Miyazaki N, Hashimoto R, Izawa T, Sakai K, Yazawa T, Iwashita M.
    • Journal Title

      Fetal Diagn Ther

      Volume: 35 Issue: 2 Pages: 148-150

    • DOI

      10.1159/000355601

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD8-positive T-cell lymphoproliferative disorder associated with Epstein-barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment.2014

    • Author(s)
      Koji H, Yazawa T, Nakabayashi K, Fujioka Y, Kamma H, Yamada A.
    • Journal Title

      Mod Rheumatol

      Volume: 24 Issue: 2 Pages: 1-5

    • DOI

      10.3109/14397595.2013.850613

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer2013

    • Author(s)
      Sakaeda M, Sato H, et al.
    • Journal Title

      Laboratory Investigation

      Volume: 93 Issue: 4 Pages: 408-421

    • DOI

      10.1038/labinvest.2013.2

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer2013

    • Author(s)
      Ishii J, Sato H, et al.
    • Journal Title

      Pathology International

      Volume: 63 Issue: 3 Pages: 158-168

    • DOI

      10.1111/pin.12042

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differences of molecular expression mechanisms among neural cell adhesion molecule 1, synaptophysin, and chrmogranin A in lung cancer cells2012

    • Author(s)
      Kashiwagi K, Ishii J, Sakaeda M, Arimasu Y, Shimoyamada H, Sato H, Miyata C, Kamma H, Aoki I, Yazawa T
    • Journal Title

      Pathol Int

      Volume: VOL.62 Issue: 4 Pages: 232-245

    • DOI

      10.1111/j.1440-1827.2011.02781.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 神経系細胞特異的転写因子の機能解析結果を基盤とした小細胞肺癌の細胞形質解析2014

    • Author(s)
      矢澤卓也
    • Organizer
      第18回日本内分泌病理学会
    • Place of Presentation
      都道府県会館(東京都・千代田区)
    • Year and Date
      2014-11-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 甲状腺髄様癌のカルシトニン産生におけるPROX1の役割について2014

    • Author(s)
      石井 順、有益 優、千葉知宏、矢澤卓也、菅間 博
    • Organizer
      第18回日本内分泌病理学会
    • Place of Presentation
      都道府県会館(東京都・千代田区)
    • Year and Date
      2014-11-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膵管癌と膵の非腫瘍性上皮の鑑別にIMP3免疫染色は有用である2014

    • Author(s)
      前田珠里、岸本 充、神戸美千代、太田 聡、米盛葉子、大出貴士、矢澤卓也、三島 敬、中臺英理、宮崎 勝、中谷行雄
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 子宮内腔、腹膜に転移を来した卵管原発明細胞癌の一例2014

    • Author(s)
      尾坂 真、秋田貴之、望月 眞、寺戸雄一、矢澤卓也、菅間 博、大倉康男、西ヶ谷順子、百村麻衣、小林陽一
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺の神経内分泌系悪性腫瘍とIII/IV型POU遺伝子2014

    • Author(s)
      石井 順、矢澤卓也、佐藤華子、宍戸-原由紀子、平松千恵、下山田博明、藤原正親、菅間 博
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 乳頭状増殖形態を呈した乳腺原発脂腺癌の一例2014

    • Author(s)
      千葉知宏、住石 歩、水谷奈津子、矢澤卓也、菅間 博
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島県・広島市)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] POU型転写因子BRN2は肺小細胞癌細胞の神経/神経内分泌形質発現および増殖活性に関与する2013

    • Author(s)
      石井順、佐藤華子、榮田昌史、原由紀子、平松千恵、菅間博、下山田博明、藤原正親、遠藤哲哉、青木一郎、矢澤卓也
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺小細胞癌におけるTTF-1発現はPOUドメイン転写因子BRN2により直接的に制御されている2013

    • Author(s)
      榮田昌史、佐藤華子、石井順、菅間博、原由紀子、平松千恵、下山田博明、藤原正親、遠藤哲哉、矢澤卓也
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺神経内分泌腫瘍におけるBRN2、ASCL1、TTF1の発現性の検討2013

    • Author(s)
      遠藤哲哉、石井順、榮田昌史、藤原正親、宍戸-原由紀子、下山田博明、平野和彦、寺戸雄一、菅間博、矢澤卓也
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] Cytokeratin 7、CEA発現性から見た肺神経内分泌腫瘍群の不均一性の検討2013

    • Author(s)
      斎藤しおり、田川祐未、對馬可菜、矢澤卓也、菅間博
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] 小細胞肺癌の細胞形質を制御する転写因子の機能解析から見えてくるもの2013

    • Author(s)
      矢澤卓也
    • Organizer
      第59回日本病理学会秋期特別総会
    • Place of Presentation
      甲府
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 肺癌の神経/神経内分泌形質にASCL1およびRESTが与える影響の解析2012

    • Author(s)
      石井順、有益優、榮田昌史、柏木維人、下山田博明、佐藤華子、宮田千恵、藤原正親、菅間博、青木一郎、矢澤卓也
    • Organizer
      第101日本病理学会総会
    • Place of Presentation
      新宿、東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 肺癌におけるThyroid transcription factor-1の発現機序に関与する因子の検索2012

    • Author(s)
      榮田昌史、佐藤華子、宮田千恵、石井順、有益優、柏木維人、下山田博明、菅間博、青木一郎、矢澤卓也
    • Organizer
      第101日本病理学会総会
    • Place of Presentation
      新宿、東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経内分泌マーカーの発現機序解析から見えてくるもの2012

    • Author(s)
      矢澤卓也
    • Organizer
      第55回日本病理学会関東支部会学術集会
    • Place of Presentation
      三鷹、東京都
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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