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Study for development of the therapy targeting the novel oncogene lipocalin2 in endometrial carcinoma

Research Project

Project/Area Number 25293339
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionShinshu University

Principal Investigator

MIYAMOTO Tsutomu  信州大学, 学術研究院医学系(医学部附属病院), 講師 (70418721)

Co-Investigator(Kenkyū-buntansha) SHIOZAWA Tanri  信州大学, 学術研究院医学系, 教授 (20235493)
KOBARA Hisanori  信州大学, 学術研究院医学系, 助教 (30598818)
YAMADA Yasushi  信州大学, 学術研究院医学系(医学部附属 病院), 助教 (60646652)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywordslipocalin2 / 子宮内膜癌 / 抗癌剤耐性 / 癌幹細胞マーカー / マイクロアレイ / 造腫瘍能
Outline of Final Research Achievements

Using luciferase-reporter assay, we demonstrated that NFκB and Ferric ion did not affect to the control of the LCN2 expression in HHUA cells. We also demonstrated that LCN2 significantly enhanced the cisplatin (CDDP) resistance by WST-1 assay using HHUA, RL95-2 and HEC1B cells. This effect was depend on ferric ion, but was independent from PI3K pathway and MAPK pathway. LCN2 significantly enhanced the anchorage-independent colony-formation ability, and enhanced the protein expression of CD44v9 and CD133, which is known as cancer stem cell markers. These results suggested that LCN2 might be involved in the maintenance and enhancement of the cancer stem cell properties, which might be inducing chemo-resistance. In addition, we found NUPR1 as a candidate for the downstream factors of LCN2 effects by microarray analysis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (17 results)

All 2016 2015 2014 2013 Other

All Journal Article (13 results) (of which Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (4 results)

  • [Journal Article] Lipocalin 2 attenuates iron-related oxidative stress and prolongs the survival of ovarian clear cell carcinoma cells by up-regulating the CD44 variant.2016

    • Author(s)
      Yamada Y, Miyamoto T, Kashima H, Kobara H, Asaka R, Ando H, Higuchi S, Ida K, Shiozawa T.
    • Journal Title

      Free Radic Res.

      Volume: 50 Issue: 4 Pages: 414-25

    • DOI

      10.3109/10715762.2015.1134795

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells.2016

    • Author(s)
      Miyamoto T, Kashima H, Yamada Y, Kobara H, Asaka R, Ando H, Higuchi S, Ida K, Mvunta DH, Shiozawa T
    • Journal Title

      PLoS One

      Volume: 11 Issue: 5 Pages: e0155220-e0155220

    • DOI

      10.1371/journal.pone.0155220

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target.2015

    • Author(s)
      Asaka R, Miyamoto T, Yamada Y, Ando H, Mvunta DH, Kobara H, Shiozawa T
    • Journal Title

      Lab Invest

      Volume: 95 Issue: 12 Pages: 1363-73

    • DOI

      10.1038/labinvest.2015.119

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.2015

    • Author(s)
      Kashima H, Wu RC, Wang Y, Sinno AK, Miyamoto T, Shiozawa T, Wang TL, Fader AN, Shih IeM.
    • Journal Title

      Gynecol Oncol.

      Volume: 139 Issue: 2 Pages: 338-44

    • DOI

      10.1016/j.ygyno.2015.08.025

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells2015

    • Author(s)
      Ke H, Suzuki A, Miyamoto T, Kashima H, Shiozawa T
    • Journal Title

      Mol Cell Endocrinol

      Volume: 400 Pages: 71-7

    • DOI

      10.1016/j.mce.2014.10.027

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent low-grade endometrial stromal sarcoma with intracaval and intracardiac tumor thrombus: diagnosis, treatment, and surgical management2014

    • Author(s)
      Miyamoto T, Tachibana R, Kobara H, Takano T, Kato H, Shimizu A, Ohya A, Uehara T, Shiozawa T.
    • Journal Title

      International Cancer Conference Journal

      Volume: 3 Issue: 1 Pages: 1-7

    • DOI

      10.1007/s13691-013-0134-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological alterations in protamine-deficient spermatozoa2014

    • Author(s)
      Utsuno H, Miyamoto T, Oka K, Shiozawa T
    • Journal Title

      Hum Reprod

      Volume: 29 Issue: 11 Pages: 2374-81

    • DOI

      10.1093/humrep/deu225

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polypoid endometriosis of the ovary mimicking ovarian carcinoma dissemination: a case report and literature review2014

    • Author(s)
      4.Yamada Y, Miyamoto T, Horiuchi A, Ohya A, Shiozawa T
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 40 Issue: 5 Pages: 1426-30

    • DOI

      10.1111/jog.12358

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA).2013

    • Author(s)
      Takatsu A, Miyamoto T, Fuseya C, Suzuki A, Kashima H, Horiuchi A, Ishii K, Shiozawa T
    • Journal Title

      Virchows Arch

      Volume: 462(6) Issue: 6 Pages: 645-51

    • DOI

      10.1007/s00428-013-1417-1

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia.2013

    • Author(s)
      Kobara H, Miyamoto T, Suzuki A, Asaka R, Yamada Y, Ishikawa K, Kikuchi N, Ohira S, Shiozawa T.
    • Journal Title

      Placenta

      Volume: 34(11) Issue: 11 Pages: 1036-43

    • DOI

      10.1016/j.placenta.2013.08.004

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Immunohistochemical expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma: a novel potential prognostic factor.2013

    • Author(s)
      Miyamoto T
    • Journal Title

      Histopathology

      Volume: Feb 9 [Epub ahead of print] Issue: 7 Pages: 986-93

    • DOI

      10.1111/his.12107

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 進行子宮頸がんの根治手術 : 術前化学療法後の広汎子宮全摘 (今月の臨床 進行婦人科がんの集学的治療) -- (子宮頸がん)2013

    • Author(s)
      宮本 強 , 塩沢 丹里
    • Journal Title

      臨床婦人科産科

      Volume: 67(11) Pages: 1099-1104

    • NAID

      40019860821

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 月経異常患者の子宮体がん予防 (今月の臨床 婦人科がんの予防戦略と早期診断) -- (子宮体がん)2013

    • Author(s)
      宮本 強 , 塩沢 丹里
    • Journal Title

      臨床婦人科産科

      Volume: 67(8) Pages: 805-812

    • NAID

      40019775961

    • Related Report
      2013 Annual Research Report
  • [Presentation] 鉄運搬に関わるLipocalin2は、子宮内膜癌で新規がん遺伝子として機能する2013

    • Author(s)
      宮本 強、浅香亮一、山田 靖、小原久典、石川香織、鈴木昭久、塩沢丹里
    • Organizer
      第65回日本産科婦人科学会学術講演会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lipocalin2は子宮内膜癌において新規癌遺伝子として作用する2013

    • Author(s)
      宮本 強、山田 靖、浅香亮一、安藤大史、石川香織、小原久典、鈴木昭久、塩沢丹里
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lipocalin2 accelerates tumor growth and functions as a novel onvogene in endometrial carcinoma cell.2013

    • Author(s)
      Miyamoto T,Yamada Y,Kobara H,Asaka R,Ando H,Ishikawa K,David Hamisi Mvunta,Suzuki A,Shiozawa T.
    • Organizer
      第3回アジア婦人科腫瘍学会・第55回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lipocalin2,an iron transporter,functions as a novel oncogene and enhances the proliferation and survival of endometrial carcinoma cell

    • Author(s)
      Miyamoto T,Asaka R, Yamada Y,Ishikawa k, Kobara H,Suzuki A,Shiozawa T.
    • Organizer
      American Assosiation for Cancer Research Annual Meeting 2013
    • Place of Presentation
      ワシントンD.C(アメリカ)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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