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2010 Fiscal Year Final Research Report

Overexpression of S100A4 is associated with DNA hypomethylation and enhanced invasiveness in ovarian carcinomas

Research Project

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Project/Area Number 20591942
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionShinshu University

Principal Investigator

KIKUCHI Norihiko  Shinshu University, 医学部・附属病院, 助教 (50447728)

Co-Investigator(Kenkyū-buntansha) HORIUCHI Akiko  信州大学, 医学部, 講師 (80334895)
FUSEYA Chiho  信州大学, 医学部・附属病院, 助教(診療) (50447736)
SHIOZAWA Tanri  信州大学, 医学部, 教授 (20235493)
Project Period (FY) 2008 – 2011
Keywords卵巣癌 / 脱メチル化 / S100A4
Research Abstract

The S100A4 protein which belongs to calcium binding S100 protein family has been suggested to be linked to metastatic phenotypes of cancer cell. In this study, we investigated the association between the expression of S100A4 and hypomethylation of the S100A4 first intron in ovarian carcinoma cells. We first used immunohistochemistry to examine the expression and localization of S100A4 in 113 epithelial ovarian neoplasms and analyzed its prognostic significance in patients with ovarian carcinoma. Ovarian carcinoma patients with strong nuclear S100A4 expression showed a significantly shorter survival than those without (p=0.0045). Three ovarian cancer cell lines (SKOV3, A2780, A2780/CDDP) expressed S100A4, however, OVCAR3 and OSEs did not. Matrigel invasion assay showed that the expression level of S100A4 was associated with invasive ability in ovarian cancer cells. The specific siRNA for S100A4 suppressed S100A4 expression and the invasiveness of A2780/CDDP cells. We then studied the relationship between DNA methylation status and S100A4 expression by bisulfite-modified DNA sequencing in ovarian cancer cell lines and 51 cases of ovarian carcinoma tissues. We found that CpG sites in the first intron of the S100A4 gene were hypomethylated in S100A4 positive ovarian carcinoma cells. In contrast, these CpG sites were methylated in S100A4 negative ovarian carcinoma cells and S100A4 expression was altered by 5-aza-2deoxycytidine treatment. In ovarian cancer tissues, 24 cases of S100A4 strongly positive were hypomethylated in the first intron of S100A4 gene and 14 of all S100A4 negative cases were methylated.

  • Research Products

    (25 results)

All 2011 2010 2009 2008

All Journal Article (20 results) (of which Peer Reviewed: 19 results) Presentation (5 results)

  • [Journal Article] Molecular Approach to Uterine Leiomyosarcoma : LMP2-Deficient Mice as an Animal Model of Spontaneous Uterine Leiomyosarcoma.2011

    • Author(s)
      Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I
    • Journal Title

      Sarcoma. 2011

      Pages: 476498

    • Peer Reviewed
  • [Journal Article] Weekly administration of temsirolimus for heavily pretreated patients with clear cell carcinoma of the ovary: a report of six cases.2011

    • Author(s)
      Takano M, Kikuchi Y, Kudoh K, Goto T, Furuya K, Kikuchi R, Kita T, FujK, Shiozawa T, Aoki D
    • Journal Title

      int J Clin Oncol

    • Peer Reviewed
  • [Journal Article] Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma : HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with down-regulation of E-cadherin.2010

    • Author(s)
      Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, Konishi I, Shiozawa T
    • Journal Title

      Int J Cancer. 127

      Pages: 1332-1346

    • Peer Reviewed
  • [Journal Article] Oct4 expression in immature teratoma of the ovary : relevance thistologic grade and degree of differentiation.2010

    • Author(s)
      Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I
    • Journal Title

      Am J Surg Pathol 34(12)

      Pages: 1842-1848

    • Peer Reviewed
  • [Journal Article] Distinguishing primary from secondary mucinous ovarian tumors : an algorithm using the novel marker DPEP1.2010

    • Author(s)
      Okamoto T, Matsumura N, Mandai M, Oura T, Yamanishi Y, Horiuchi A, Hamanishi J, Baba T, Koshiyama M, Shiozawa T, Konishi I
    • Journal Title

      Mod Pathol. Nov 12.

    • Peer Reviewed
  • [Journal Article] Cyclin A2 confers cisplatin resistance to endometrial carcinoma cells via up-regulation of an Akt-binding protein, periplakin.2010

    • Author(s)
      Suzuki A, Horiuchi A, Ashida T, Miyamoto T, Kashima H, Nikaido T,Konishi I, Shiozawa T
    • Journal Title

      J Cell Mol Med. 14(9)

      Pages: 2305-2317

    • Peer Reviewed
  • [Journal Article] Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma.2010

    • Author(s)
      Hayashi T, Horiuchi A, Sano K, Hi N, Kanai Y, Shiozawa T, Tonegawa S Konishi I
    • Journal Title

      Protein Cell. 1(8)

      Pages: 711-717

    • Peer Reviewed
  • [Journal Article] Immunohistochemical detection of histone deacetylases in endometrial carcinoma : involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells.2010

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

      Hum Pathol 41(6)

      Pages: 848-858

    • Peer Reviewed
  • [Journal Article] Immunohistochemical detectiosteroid receptor cofactors in ovarianendometriosis : involvement of down-regulated SRC-1 expression in the limited growth activity of the endometriotic epithelium.2010

    • Author(s)
      Suzuki A, Horiuchi A, Oka K, Miyamoto T, Kashima H, Shiozawa T
    • Journal Title

      Virchows Arch 456(4)

      Pages: 433-441

    • Peer Reviewed
  • [Journal Article] Tumor immunoediting: from immunosurveillance to tumor escape-in case of uterine leiomyosarcoma^-.Current Res.2010

    • Author(s)
      Hayashi T, Kobayashi Y, Horiuchi A, Hiraoka N, Kanai Y, AburataTonegawa S, Konishi I, Sano K.
    • Journal Title

      Immunol.

    • Peer Reviewed
  • [Journal Article] Fetal goitrous hypothyroidism due to maternal thyroid stimulation-blocking antibody : a case report.2010

    • Author(s)
      Ohira S, Miyake M, Kobara H, Kikuchi N, Osada R, Ashida T, Hirabayashi Nishio S, Kanai M, Shiozawa T
    • Journal Title

      Fetal Diagn Ther. 28(4)

      Pages: 220-224

    • Peer Reviewed
  • [Journal Article] Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer : a proposal for partient selection.2010

    • Author(s)
      Satoh T, Hatae M, Watanabe Y, Yaegashi N, Ishiko O, Kodama S, Yamaguchi S, Ochiai K, Takano M, Yokota H, Kawakami Y, Nishimura S, Ogishima D, Nakagawa S, Kobayashi H, Shiozawa T, Nakanishi T, Kamura T, Konishi I, Yoshikawa
    • Journal Title

      J Clin Oncol. 28(10)

      Pages: 1727-1732

    • Peer Reviewed
  • [Journal Article] 卵巣癌腹膜播種性転移の分子機序2010

    • Author(s)
      堀内晶子、布施谷千穂、林晶子、菊地彦、塩沢丹里
    • Journal Title

      産婦人科の実際 vol.59 No.10

      Pages: 1501-1508

    • Peer Reviewed
  • [Journal Article] 卵巣癌発生の自然史と早期診断2010

    • Author(s)
      堀内晶子、塩沢丹里
    • Journal Title

      信州医誌 48

      Pages: 143-151

    • Peer Reviewed
  • [Journal Article] Inverse correlation between Skp2 and p27(Kip1) in normal endometrium and endometrial carcinoma.2009

    • Author(s)
      Miyamoto T, Horiuchi A, Kashima HSuzuki A, Yamada T, Kurai M, Konishi I, Shiozawa T
    • Journal Title

      gynecol Endocrinol 31

      Pages: 1-10

    • Peer Reviewed
  • [Journal Article] Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma: the important role of Snail in ovarian tumorigenesis and progression.2009

    • Author(s)
      Yoshida J, Horiuchi A, Kikuchi N, Hayashi A, Osada R, Ohira S, Shiozawa T, Konishi I.
    • Journal Title

      Med Mol Morphol. 42(2)

      Pages: 82-91

    • Peer Reviewed
  • [Journal Article] Autocrine stimulation of IGF1 in estrogen-induced growth of endometrial carcinoma cells: involvement of the mitogen-activated protein kinase pathway followed by up-regulation of cyclin D1 and cyclin E.2009

    • Author(s)
      Kashima H, Shiozawa T, Miyamoto T, Suzuki A, Uchikawa J, Kurai M, Konishi I.
    • Journal Title

      Endocr Relat Cancer. 16(1)

      Pages: 113-122

    • Peer Reviewed
  • [Journal Article] Up-regulation of nuclear receptor corepressor (NCoR) in progestin-induced growth suppression of endometrial hyperplasia and carcinoma.2009

    • Author(s)
      Kashima H, Horiuchi A, Uchikawa J, Miyamoto T, Suzuki A, Ashida T, Konishi I, Shiozawa T
    • Journal Title

      Anticancer Res. 29(4)

      Pages: 1023-1029

    • Peer Reviewed
  • [Journal Article] Overexpression of RhoA enhanceperitoneal dissemination : RhoA suppression with Lovastatin may be useful for ovarian cancer2008

    • Author(s)
      Horiuchi A, Kikuchi N, Osada R, Wang C, Hayashi A, Nikaido T, Konishi I
    • Journal Title

      Cancer Sci. 99(12)

      Pages: 2532-2539

    • Peer Reviewed
  • [Journal Article] 卵巣癌の発生および進展のエピジェネティクス解析-BRCA1メチル化およびS100A4脱メチル化の臨床的意義2008

    • Author(s)
      堀内晶子
    • Journal Title

      日本産科婦人科学会雑誌 60

      Pages: 1844-1854

  • [Presentation] 妊娠10週から〓胞状エコー像が出現したplacental mesenchymal dysplasiaの1例2010

    • Author(s)
      大平哲史、大久保奈緒、山崎悠紀、小野恭子、小原久典、菊地範彦、金井誠、塩沢丹里
    • Organizer
      第18回日本胎盤学会学術集会
    • Place of Presentation
      熊本
    • Year and Date
      2010-09-30
  • [Presentation] Possible role of hypoxia in ovarian cancer progression Special Oncology Seminar on "Hypoxia and Cancer"2010

    • Author(s)
      堀内晶子
    • Organizer
      婦人科腫瘍学セミナー京都大学医学研究科がんプロフェッショナル養成プラン事業
    • Place of Presentation
      京都
    • Year and Date
      2010-06-07
  • [Presentation] 卵巣癌における癌抑制遺伝子Int6およびhypoxia inducible factor(HIF)-αサブユニット発現の検討2010

    • Author(s)
      長田亮介、堀内晶子、林晶子、布施谷千穂、菊地範彦、三橋祐布子、塩沢丹里
    • Organizer
      第62回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-23
  • [Presentation] 低酸素環境卵巣癌細胞においてS100A4発現はHypoxia-inducible factor-1αを介し亢進する2008

    • Author(s)
      菊地範彦、堀内晶子、林琢磨、林晶子、長田亮介、布施谷千穂、塩沢丹里、小西郁生
    • Organizer
      第60回日本産科婦人科学会・学術講演会ポスター
    • Place of Presentation
      東京
    • Year and Date
      2008-04-15
  • [Presentation] 卵巣癌の発生および進展のエピジェネティクス解析-BRCA1メチル化およびS100A4脱メチル化の臨床的意義(シンポジウム口演)2008

    • Author(s)
      堀内晶子
    • Organizer
      第60回日本産科婦人科学会・学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2008-04-14

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Published: 2012-01-26   Modified: 2016-04-21  

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