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Development of a biomarker in gynecologic cancer to predict outcome with abnormal expression of cell polarity molecules.

Research Project

Project/Area Number 24592506
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

NAGASAKA KAZUNORI  東京大学, 医学部附属病院, 助教 (30624233)

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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords細胞極性制御機構 / バイオマーカー / 網羅的解析 / 転写産物 / 脱リン酸化酵素 / 細胞極性決定因子 / リン酸化機構 / 網羅的転写産物解析 / 子宮頸癌 / ヒトパピローマウイルス / 発癌メカニズム / 転写物 / ノンコーディングRNA / 国際情報交換
Outline of Final Research Achievements

We performed CAGE (Cap Analysis Gene Expression) analysis to investigated transcriptome start sites (TSSs) from the perspective of both the HPV and human genomes. The result showed that the cell polarity and adhesion pathway is dramatically downregulated, and we found a novel antisense viral transcript only seen in CIN cervical cells. Using the molecular and biochemical analyses, we found that cell polarity protein hScrib regulates Ras-ERK pathway, and the activity is mediated in part through recruitment of protein phosphatase 1γ (PP1γ). Furthermore, we have explored the potential role of PP1γ in HPV-induced cervical malignancy. Then, we have found a striking concordance with cellular redistribution in pattern of expression, and this loss of PP1γ expression and redistribution in pattern of expression occurs progressively as the lesions develop. Taken together, we have concluded that PP1γ would be a novel biomarker to predict disease progression for HPV induced malignancy.

Report

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

    (21 results)

All 2015 2014 2013 2012

All Journal Article (14 results) (of which Peer Reviewed: 12 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Characterization of novel transcripts of human papillomavirus type 16 using cap analysis gene expression technology2015

    • Author(s)
      Taguchi A, Nagasaka K, Kawana K, Hashimoto K, Kusumoto-Matsuo R, Plessy C, Miranda T, Nakamura H, Bonetti A, Oda K, Kukimoto I, Carninci P, Banks L, Osuga Y, Fujii T,
    • Journal Title

      J Virol

      Volume: 89 Issue: 4 Pages: 2448

    • DOI

      10.1128/jvi.03433-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HPV-16 impairs the subcellular distribution and levels of expression of protein phosphatase 1γ in cervical malignancy2015

    • Author(s)
      Seiki T, Nagasaka K, Kranjec C, Kawana K, Maeda D, Nakamura H, Taguchi A, Matsumoto Y, Arimoto T, Wada-Hiraike O, Oda K, Nakagawa S, Yano T, Fukayama M, Banks L, Osuga Y, Fujii T.
    • Journal Title

      BMC Cancer

      Volume: 15 Issue: 1 Pages: 230-230

    • DOI

      10.1186/s12885-015-1141-0

    • NAID

      120007089068

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] High-risk human papillomavirus correlates with recurrence after laser ablation for treatment of patients with cervical intraepithelial neoplasia 3: A long-term follow-up retrospective study2014

    • Author(s)
      Inaba K, Nagasaka K, Kawana K, Arimoto T, Matsumoto Y, Tsuruga T, Mori-Uchino M, Miura S, Sone K, Oda K, Nakagawa S, Yano T, Kozuma S, Fujii T
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 40 Issue: 2 Pages: 554

    • DOI

      10.1111/jog.12196

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive peritoneal cytology at interval surgery is a poor prognostic factor in patients with stage T3c advanced ovarian carcinoma: A retrospective study2014

    • Author(s)
      Nagasaka K, Kawana K, Tomio K, Eguchi S, Miura S, Tsuruga T, Mori-Uchino M, Tanikawa M, Tsukazaki T, Sone K, Adachi K, Matsumoto Y, Arimoto T, Oda K, Osuga Y, Fujii T
    • Journal Title

      J Obstet Gynecol Res

      Volume: 41 Issue: 5 Pages: 755

    • DOI

      10.1111/jog.12616

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo2014

    • Author(s)
      Taguchi A, Kawana K, Tomio K, Yamashita A, Isobe Y, Nagasaka K, Koga K, Inoue T, Nishida H, kojima S, Adachi K, Matsumoto Y, Arimoto T, Wada-Hiraike O, Oda K, kang JX, Arai H, Arita M, Osuga Y, Fujii T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 2 Pages: e89605-e89605

    • DOI

      10.1371/journal.pone.0089605

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-tumor activity of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in cultured endometrial carcinoma cells2014

    • Author(s)
      A. Miyasaka, K. Oda, Y. Ikeda, O. Wada-Hiraike, T. Kashiyama, A. Enomoto, N. Hosoya, T. Koso, T. Fukuda, K. Inaaba, K. Sone, Y. Uehara, R. Kurikawa, K. Nagasaka, Y.Matsumoto, T. Arimoto, S. Nakagawa, H. Kuramoto, K. Miyagawa, T. Yano, K. Kawana, Y. Osuga, T. Fujii.
    • Journal Title

      BMC Cancer

      Volume: 14 Issue: 1 Pages: 179-179

    • DOI

      10.1186/1471-2407-14-179

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer2013

    • Author(s)
      Ikeda Y, Oda K, Hiraike-Wada O, Koso T, Miyasaka A, Kashiyama T, Tanikawa M, Sone K, Nagasaka K, Maeda D, Kawana K, Nakagawa S, Fukayama M, Tetsu O, Fujii T, Yano T, Kozuma S
    • Journal Title

      Oncol Rep

      Volume: 30 Issue: 2 Pages: 584

    • DOI

      10.3892/or.2013.2515

    • NAID

      120007089077

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PDZ domains and viral infection: Versatile potentials of hpv-pdz interactions in relation to malignancy2013

    • Author(s)
      Nagasaka K, Kawana K, Osuga Y, Fujii T.
    • Journal Title

      BioMed research international

      Volume: 2013 Pages: 369712-369712

    • DOI

      10.1155/2013/369712

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth2013

    • Author(s)
      Yamashita A, Kawana K, Tomio K, Taguchi A, Isobe Y, Iwamoto R, Masuda K, Furuya H, Nagamatsu T, Nagasaka K, Oda K, Wada-Hiraike O, Yamashita T, Taketani Y, Kang JX, Arai H, Arita M, Kozuma S, Fujii T.
    • Journal Title

      Sci Rep

      Volume: 3 Issue: 1 Pages: 3113-3113

    • DOI

      10.1038/srep03113

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Novel Interaction between hScrib and PP1γ Downregulates ERK Signaling and Suppresses Oncogene-Induced Cell Transformation2013

    • Author(s)
      Nagasaka K, Seiki T, Yamashita A, Massimi P, Subbaiah VK, Thomas M, Kranjec C, Kawana K, Nakagawa S, Yano T, Taketani Y, Fujii T, Kozuma S, Banks L
    • Journal Title

      PLosOne

      Volume: 8 Issue: 1 Pages: 53752-53760

    • DOI

      10.1371/journal.pone.0053752

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sequential effects of the proteasome inhibitor bortezomib and chemotherapeutic agents in uterine cervical cancer cell lines2013

    • Author(s)
      Miyamoto Y, Nakagawa S, Wada-Hiraike O, Seiki T, Tanikawa M, Hiraike H, Sone K, Nagasaka K, Oda K, Kawana K, Nakagawa K, Fujii T, Yano T, Kozuma S, Taketani Y.
    • Journal Title

      Oncol Rep.

      Volume: 29 Issue: 1 Pages: 51

    • DOI

      10.3892/or.2012.2072

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Prevalence Of Cervical Regulatory T Cells in HPV-Related Cervical Intraepithelial Neoplasia (CIN) Correlates Inversely with Spontaneous Regression of CIN2013

    • Author(s)
      Kojima S, Kawana K, Tomio K, Yamashita A, Taguchi A, Nagamatsu T, Nagasaka K, Matsumoto Y, Arimoto T, Oda K, Wada-Hiraike O, Yano T, Taketani Y, Fujii T, Schust DJ, Kozuma S
    • Journal Title

      Am J Reprod Immunol,

      Volume: 69 Issue: 2 Pages: 134

    • DOI

      10.1111/aji.12030

    • URL

      https://pure.teikyo.jp/en/publications/57ac5306-26d0-4646-ad14-8521673ad284

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 性感染症の現状と治療の問題点 8. HPVワクチン2012

    • Author(s)
      長阪一憲、川名敬
    • Journal Title

      化学療法の領域 5月号

      Volume: 7 Pages: 97-104

    • Related Report
      2012 Research-status Report
  • [Journal Article] ヒトパピローマウイルスワクチンの効果2012

    • Author(s)
      長阪一憲、川名敬
    • Journal Title

      バムサジャーナル

      Volume: 2 Pages: 3-9

    • NAID

      40019386632

    • Related Report
      2012 Research-status Report
  • [Presentation] HPV検査と細胞診の臨床的意義:HPV life cycleの視点から2014

    • Author(s)
      長阪一憲
    • Organizer
      日本臨床細胞学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2014-11-02 – 2014-11-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CINから子宮頸癌への癌進展制御に関わるHPV由来の新規non-coding RNAの同定とその機能解析2014

    • Author(s)
      田口歩、川名敬、長阪一憲、橋本浩介、西田晴香、井上知子、松本陽子、有本貴英、平池修、織田克利、大須賀穣、藤井知行
    • Organizer
      日本産婦人科学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] HPV16 E6 interferes with hScrib regulation of ERK through protein phosphatase 1γ2013

    • Author(s)
      Kazunori Nagasaka
    • Organizer
      DNA Tumour Virus Meeting 2013
    • Place of Presentation
      Birmingham, UK
    • Related Report
      2013 Research-status Report
  • [Presentation] Analysis of HPV-induced transcriptional network by deep-CAGE sequencing in different HPV16-positive cell-lines and cervical cancer specimens2013

    • Author(s)
      Kazunori Nagasaka
    • Organizer
      DNA Tumour Virus Meeting 2013
    • Place of Presentation
      Birmingham, UK
    • Related Report
      2013 Research-status Report
  • [Presentation] 細胞極性決定因子hScribは脱リン酸化蛋白Protein phosphatase-1 gammaとの結合を介してERK系路を制御する2012

    • Author(s)
      長阪一憲、川名敬、田口歩、清木孝之、山下亜紀、宮本雄一郎、曾根献文、松本陽子、平池修、織田克利、中川俊介、矢野哲、武谷雄二
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Book] 臨床検査ガイド20152015

    • Author(s)
      長阪一憲 矢野哲
    • Publisher
      文光堂
    • Related Report
      2014 Annual Research Report
  • [Book] 臨床検査ガイド2013-2014 ヒトパピローマウイルスDNA検査2013

    • Author(s)
      長阪一憲 矢野哲
    • Publisher
      文光堂
    • Related Report
      2012 Research-status Report

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

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