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Functional analysis of GPR30 in cervical adenocarcinoma

Research Project

Project/Area Number 17K08698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

Takasawa Akira  札幌医科大学, 医学部, 講師 (00593021)

Co-Investigator(Kenkyū-buntansha) 村田 雅樹  札幌医科大学, 医学部, 講師 (10404592)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords子宮頸部腺がん / エストロゲン受容体 / GPR30 / 病理学 / 子宮頸部 / 子宮頸部腺癌 / エストロゲン / 子宮頚部
Outline of Final Research Achievements

The expression of GPR30 was analyzed in the surgical specimen of uterine cervical adenocarcinoma. GPR30 was significantly high expressed in adenocarcinoma than in non-tumor glandular epithelium. Patients with each higher GPR30 and claudin-1 expression had a worse prognosis. GPR30 and ER expression were negatively correlated, suggesting that ER may function as an estrogen receptor in normal glandular epithelium and GPR30 in adenocarcinoma tissue. We identified several proteins that increase with GPR30 agonist exposure to several cell lines. When protein X was deleted by the CRISPR-Cas9 system, proliferation ability and the like were remarkably suppressed. It was suggested that GPR30 may be involved in malignant transformation of cervical adenocarcinoma via multiple proteins.

Academic Significance and Societal Importance of the Research Achievements

子宮頸部腺がんは、予後が悪く、患者数が増加しているものの、その自然史は十分に理解されていない。本研究では、頸部腺がんの悪性化に関与する機序の一部が明らかになった。特に、古典的エストロゲン受容体が発現していないことから、エストロゲン非依存性癌と理解されてきた頸部腺がんに、膜型エストロゲン受容体GPR30が発現し、claudin-1を介して悪性化に関与していることを明らかにした。この結果は、頸部腺がんがエストロゲン依存性癌である可能性を示すものであり、頸部腺がん患者の治療戦略を変える可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (29 results)

All 2020 2019 2018 2017 2016

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Elevated expression of G protein-coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma.2020

    • Author(s)
      Ino Y, Akimoto T, Takasawa A, Takasawa K, Aoyama T, Ueda A, Ota M, Magara K, Tagami Y, Murata M, Hasegawa T, Saito T, Sawada N, Osanai M.
    • Journal Title

      Histol Histopathol

      Volume: 35 Pages: 351-359

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoreactivity patterns of tight junction proteins are useful for differential diagnosis of human salivary gland tumors.2019

    • Author(s)
      Aoyama T, Takasawa A, Murata M, Osanai M, Takano K, Hasagawa T, Sawada N.
    • Journal Title

      Med Mol Morphol.

      Volume: 52 Issue: 1 Pages: 23-35

    • DOI

      10.1007/s00795-018-0199-6

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of Coiled-Coil Domain-Containing Protein 180 and Leucine-Rich Repeat-Containing Protein 4 as Potential Immunohistochemical Markers for Liposarcoma Based on Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded Tissue.2019

    • Author(s)
      Aoyama T, Takasawa A, Takasawa K, Ono Y, Emori M, Murata M, Hayasaka T, Fujitani N, Osanai M, Yamashita T, Hasegawa T, Sawada N.
    • Journal Title

      Am J Pathol.

      Volume: in press Issue: 5 Pages: 1015-1028

    • DOI

      10.1016/j.ajpath.2019.01.013

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells2019

    • Author(s)
      Hayasaka Naotaka、Takada Kohichi、Nakamura Hajime、Arihara Yohei、Kawano Yutaka、Osuga Takahiro、Murase Kazuyuki、Kikuchi Shohei、Iyama Satoshi、Emori Makoto、Sugita Shintaro、Hasegawa Tadashi、Takasawa Akira、Miyanishi Koji、Kobune Masayoshi、Kato Junji
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 5759-5759

    • DOI

      10.1038/s41598-019-42300-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of valgus laxity after release of the medial structure in medial open-wedge high tibial osteotomy: an in vivo biomechanical study using quantitative valgus stress radiography.2019

    • Author(s)
      Sato D, Kondo E, Yabuuchi K, Onodera J, Onodera T, Yagi T, Sakamoto K, Takasawa A, Iwasaki N, Yasuda K.
    • Journal Title

      BMC Musculoskelet Disord

      Volume: 20 Issue: 1 Pages: 481-481

    • DOI

      10.1186/s12891-019-2859-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen/GPR30 signaling contributes to the malignant potentials of ER-negative cervical adenocarcinoma via regulation of claudin-1 expression2018

    • Author(s)
      Akimoto T, Takasawa A, Takasawa K, Aoyama T, Murata M, Osanai M, Saito T, Sawada N
    • Journal Title

      Neoplasia

      Volume: 10 Issue: 10 Pages: 1083-1093

    • DOI

      10.1016/j.neo.2018.08.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytotoxicity of Clostridium perfringens enterotoxin depends on the conditions of claudin-4 in ovarian carcinoma cells2018

    • Author(s)
      Tanaka S, Aoyama T, Ogawa M, Takasawa A, Murata M, Osanai M, Saito T, Sawada N
    • Journal Title

      Exp Cell Res

      Volume: 371 Issue: 1 Pages: 278-286

    • DOI

      10.1016/j.yexcr.2018.08.024

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Retinoic acid-metabolizing enzyme CYP26A1 promotes skin carcinogenesis induced by DMBA2018

    • Author(s)
      Osanai M, Takasawa A, Takasawa K, Murata M, Sawada N
    • Journal Title

      Oncol Lett

      Volume: 15 Pages: 9987-9993

    • DOI

      10.3892/ol.2018.8599

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic significance of the co-expression of EGFR and HER2 in adenocarcinoma of the uterine cervix.2017

    • Author(s)
      Ueda A, Takasawa A, Akimoto T, Takasawa K, Aoyama T, Ino Y, Nojima M, Ono Y, Murata M, Osanai M, Hasegawa T, Saito T, Sawada N.
    • Journal Title

      PLoS One

      Volume: 12(8) Issue: 2 Pages: 172-180

    • DOI

      10.1016/j.yexcr.2018.03.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytological findings of langerhans cell sarcoma in a case of quintuple cancer.2017

    • Author(s)
      Tabata S, Murata M, Takasawa A, Fukuda A, Ogasawara J, Koseki T, Nakano K, Segawa K, Morita R, Hasegawa T, Sawada N.
    • Journal Title

      Diagn Cytopathol.

      Volume: 45(5) Issue: 5 Pages: 441-445

    • DOI

      10.1002/dc.23628

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudin-18 coupled with EGFR/ERK signaling contributes to the malignant potentials of bile duct cancer.2017

    • Author(s)
      Takasawa K, Takasawa A, Osanai M, Aoyama T, Ono Y, Kono T, Hirohashi Y, Murata M, Sawada N.
    • Journal Title

      Cancer Lett.

      Volume: 403 Pages: 66-73

    • DOI

      10.1016/j.canlet.2017.05.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of the co-expression of EGFR and HER2 in adenocarcinoma of the uterine cervix2017

    • Author(s)
      Ueda A. Takasawa A. Akimoto T, Takasawa K, Aoyama T, Ino Y, Nojima N, Ono Y, Murata M, Osanai M, Hasegawa T, Sawana N
    • Journal Title

      PLoS ONE

      Volume: 12 Issue: 8 Pages: e0184123-e0184123

    • DOI

      10.1371/journal.pone.0184123

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated expression of JAM-A promotes neoplastic properties of lung adenocarcinoma.2017

    • Author(s)
      Magara K, Takasawa A, Osanai M, Ota M, Tagami Y, Ono Y, Takasawa K, Murata M, Hirohashi Y, Miyajima M, Yamada G, Hasegawa T, Sawada N.
    • Journal Title

      Cancer Sci.

      Volume: 108(11) Issue: 11 Pages: 2306-2314

    • DOI

      10.1111/cas.13385

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudins in cancer: bench to bedside2016

    • Author(s)
      Makoto Osanai, Akira Takasawa, Masaki Murata, Norimasa Sawada
    • Journal Title

      Pflugers Archiv

      Volume: - Issue: 1 Pages: 55-67

    • DOI

      10.1007/s00424-016-1877-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] がんにおいて異常発現するタイト結合タンパク質の機能解析と治療標的としての可能性.2019

    • Author(s)
      髙澤啓
    • Organizer
      第60回組織細胞化学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 子宮頸部腺がんにおけるエストロゲン/GPR30/claudin-1を介したがん悪性化機構の解明2019

    • Author(s)
      髙澤啓
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Estrogen/GPR30 contributes to malignant potentials of uterine cervical adenocarcinoma via claudin-1 expression.2019

    • Author(s)
      髙澤啓
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Unexpected estrogen response mediated by a membrane-bound type estrogen receptor GPR30 promotes malignant potentials of uterine cervical adenocarcinoma via regulation of claudin-1 expression.2019

    • Author(s)
      Takasawa A, Takasawa K, Osanai M.
    • Organizer
      11th AACR-JCA Joint Conference on breakthroughs in cancer research 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Unexpected estrogen response mediated by a membrane-bound type estrogen receptor GPR30 promotes malignant potentials of uterine cervical adenocarcinoma via regulation of claudin-1 expression2019

    • Author(s)
      Akira Takasawa, Kumi Takasawa, Makoto Osanai
    • Organizer
      The 11th JCA-AACR Special Joint Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of claudin-18 on malignant potentials of bile duct cancer2019

    • Author(s)
      Kumi Takasawa, Akira Takasawa, Makoto Osanai
    • Organizer
      The 11th JCA-AACR Special Joint Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] がんにおいて異常発現するタイト結合関連タンパク質の機能解析2018

    • Author(s)
      高澤啓
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 腫瘍におけるタイト結合ー細胞生物学から臨床までー2018

    • Author(s)
      高澤啓
    • Organizer
      第64回日本病理学会秋期特別総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] FFPE組織を用いた比較プロテオミクスによる高分化型脂肪肉腫のバイオマーカー探索2018

    • Author(s)
      高澤啓、長谷川匡、小山内誠
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮頸部腺癌におけるALDOAの発現とその臨床病理学的意義2018

    • Author(s)
      齋藤裕己、高澤啓、青山智志、高澤久美、小野祐輔、村田雅樹、小山内誠、澤田典均
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] FFPE組織を用いたLC-MS/MSにより原因蛋白質同定に至った心アミロイドーシスの1剖検例2018

    • Author(s)
      青山智志、高澤啓、上田朝子、小野祐輔、村田雅樹、小山内誠
    • Organizer
      第6回日本アミロイドーシス研究会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮頸部腺癌におけるJAM-A発現とその意義2018

    • Author(s)
      村上太郎、高澤啓、齋藤裕己、青山智志、小野祐輔、村田雅樹、小山内誠、澤田典均
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Overexpression of claudin-18 contributes to malignant potentials of bile duct cancer2018

    • Author(s)
      高澤久美、高澤啓、小山内誠、青山智志、小野祐輔、村田雅樹、澤田典均
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 平滑筋肉腫のFFPE組織標本を用いた新規バイオマーカー探索の試み2017

    • Author(s)
      高澤 啓、伊野 善彦、青山智志、秋元 太志、中西 敬太郎、村田 雅樹、小山内 誠、長谷川 匡、澤田 典均
    • Organizer
      第106回日本病理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Claudin-18 coupled with EGFR/ERK signaling contributes to the malignant potentials of bile duct cancer2017

    • Author(s)
      Akira Takasawa, Kumi Takasawa, Makoto Osanai, Tomoyuki Aoyama, Yusuke Ono, Tsuyoshi Kono, Yoshihiko Hirohashi, Masaki Murata, Norimasa Sawada
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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