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The expression of mammalian tumor suppressor, Int6 and hypoxia inducible factor(HIF)-2α in ovarian carcinomas

Research Project

Project/Area Number 20591941
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

OHIRA Satoshi (2010)  Shinshu University, 医学部附属病院, 助教 (90397315)

長田 亮介 (2008-2009)  Shinshu University, 医学部附属病院, 助教 (80418722)

Co-Investigator(Kenkyū-buntansha) OSADA Ryousuke  信州大学, 医学部附属病院, 助教 (80418722)
HORIUCHI Akiko  信州大学, 医学部, 講師 (80334895)
SHIOZAWA Tanri  信州大学, 医学部, 教授 (20235493)
大平 哲史  信州大学, 医学部附属病院, 助教 (90397315)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords卵巣癌 / Int6 / HIF / VHL / INT6
Research Abstract

In order to elucidate the possible involvement of Int6 in ovarian carcinomas, we examined the immunohistochemical expression of Int6, HIF-2α and von Hippel-Lindau (VHL) in ovarian carcinomas, and analyzed the prognostic differences according to Int6, HIF-2α and VHL expression in ovarian carcinoma patients. We examined the immunohistochemical expression of Int6, HIF-2α, and VHL in 70 cases of ovarian carcinomas. In addition, we analyzed the correlation and prognostic differences according to the expression of Int6, HIF-2α and VHL. We found that Int6 and VHL protein were expressed in the cytoplasm of tumor cells. Although the HIF-2α staining was mainly observed in the cytoplasm, nuclear staining was sporadically observed in ovarian carcinoma cells. Cytoplasmic expression of HIF-2α was significantly higher in tumors of FIGO stage III+IV than those of stage I+II. In advanced cases, HIF-2α expression showed inverse correlation with the expression of Int6. There was no significant correlation between HIF-2α and VHL expression. The log-rank test showed that the cytoplasmic positive HIF-2α immunostaining in tumor cells is associated with the poor prognosis of ovarian carcinoma patients (p=0.005). Interestingly, the prognosis was significantly poorer in those with positive HIF-2α and negative Int6 immunostaining. These results show that the increased expression of HIF-2α subunit and decreased expression of Int6 may involved in the progression of ovarian carcinoma.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (44 results)

All 2011 2010 2009 2008

All Journal Article (28 results) (of which Peer Reviewed: 25 results) Presentation (16 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.

      Pages: 476498-476498

    • Related Report
      2010 Final Research Report
    • 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, Fujiwara K, Shiozawa T, Aoki D.
    • Journal Title

      Int J Clin Oncol.

    • NAID

      10030247109

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic 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

    • Related Report
      2010 Final Research Report
    • 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.

    • Related Report
      2010 Final Research Report
    • 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 I, Shiozawa T
    • Journal Title

      Int J Cancer. 127(6)

      Pages: 1332-1346

    • Related Report
      2010 Final Research Report
    • 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

    • Related Report
      2010 Final Research Report
    • 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, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I.
    • Journal Title

      Protein Cell. 1(8)

      Pages: 711-717

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical detection of steroid receptor cofactors in ovarian endometriosis : 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

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor immunoediting : from immunosurvei I lance to tumor escape-in case of uterine leiomyosarcoma-.2010

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

      Current Res.Immunol. Inpress.

    • Related Report
      2010 Final Research Report
    • 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

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

    • Author(s)
      Satoh T, Hatae M, Watanabe Y, Yaegashi N, Ishiko 0, 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 H
    • Journal Title

      J Clin Oncol. 28(10)

      Pages: 1727-1732

    • Related Report
      2010 Final Research Report
    • 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 K, Nishio S, Kanai M, Shiozawa T
    • Journal Title

      Fetal Diagn Ther. 28(4)

      Pages: 220-224

    • NAID

      120007107374

    • Related Report
      2010 Final Research Report
    • 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、菊地範彦、塩沢丹里
    • Journal Title

      産婦人科の実際 vol.59 No.10

      Pages: 1501-1508

    • Related Report
      2010 Final Research Report
  • [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

    • NAID

      130004810154

    • Related Report
      2010 Final Research Report
    • 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、菊地範彦、塩沢丹里
    • Journal Title

      産婦人科の実際

      Volume: vol.59 Pages: 1501-1508

    • Related Report
      2010 Annual Research Report
  • [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

      Volume: 58 Pages: 143-151

    • NAID

      130004810154

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type-specific roles of histone deacetylase (HDAC) overexpres sion in ovarian carcinoma : HDAC1 enhances cell proliferation , 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

      Volume: 127 Pages: 1332-46

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical detection of steroid receptor cofactors in ovarian endometriosis : involvement of down-regulated SRC-1 expression in the limited growth activity of the endometri otic epithelium.2010

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

      Virchows Arch.

      Volume: 456 Pages: 433-41

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

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

      J Cell Mol Med.

      Volume: 14 Pages: 2305-17

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oct4 expression in immature teratoma of the ovary : relev ance to histologic grade , 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.

      Volume: 34 Pages: 1842-8

    • Related Report
      2010 Annual Research Report
    • 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 downregulation 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 Jan 4(Epub ahead of print)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inverse correlation between Skp2 and p27(Kipl) in normal endometrium and endometrial carcinoma.2009

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

      Gynecol Endocrinol.

      Pages: 1-10

    • Related Report
      2010 Final Research Report
    • 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

    • NAID

      10025859893

    • Related Report
      2010 Final Research Report
    • 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 Dl 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

    • Related Report
      2010 Final Research Report
    • 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

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of RhoA enhances peritoneal dissemination : RhoA suppression with Lovastatin may be useful for ovarian cancer.2009

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

      Cancer Sci. 99(12)

      Pages: 2532-2539

    • NAID

      10024014761

    • Related Report
      2010 Final Research Report
    • 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

      Pages: 82-91

    • NAID

      10025859893

    • Related Report
      2009 Annual Research Report
    • 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

    • NAID

      110006990222

    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] 妊娠10週から嚢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
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] HDAC inhibitors increased the efficacy of anticancer agent in ovarian cancer cells2010

    • Author(s)
      Akiko Hayashi, Akiko Horiuchi, Chiho Fuseya, Norihiko Kikuchi, Satoshi Ohira, Tanri Shiozawa.
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 卵巣癌発生のNatural Historyと早期診断2010

    • Author(s)
      堀内晶子
    • Organizer
      JSAWI2010
    • Place of Presentation
      淡路
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 子宮筋層内に腫瘤を形成した子宮体部明細胞腺癌の一例2010

    • Author(s)
      樋口正太郎、鈴木昭久、橘涼太、鹿島大靖、宮本強、堀内晶子、塩沢丹里
    • Organizer
      第48回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      つくば
    • Year and Date
      2010-07-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Possible role of hypoxia in ovarian cancer progression Special Oncology Seminar on "Hypoxia and Cancer"婦人科腫瘍学セミナー2010

    • Author(s)
      堀内晶子
    • Organizer
      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
    • Related Report
      2010 Final Research Report
  • [Presentation] Possible role of hypoxia in ovarian cancer progression Special Oncology Seminar on "Hypoxia, Cancer"2010

    • Author(s)
      Akiko Horiuchi
    • 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
    • Related Report
      2010 Annual Research Report
  • [Presentation] 卵巣癌における癌抑制遺伝子lnt6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、林品子、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
    • Related Report
      2010 Final Research Report
  • [Presentation] 卵巣癌における癌抑制遺伝子Int6およびhypoxia induciblefactor(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
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hypoxia induced S100A4 expression in ovarian cancer cell : S100A4 expression is a poor prognostic factor for ovarian cancer patients2009

    • Author(s)
      Horiuchi A, Kikuchi N, Hayashi A, Fuseya C, Konishi I, Shiozawa T
    • Organizer
      The 7th annual meeting of Japanese association for cancer and hypoxia research
    • Place of Presentation
      京都
    • Year and Date
      2009-12-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] 卵巣癌においてHDAC1抑制は細胞周期調節因子を介して細胞増殖を抑制する2009

    • Author(s)
      林晶子、堀内晶子、長田亮介、菊地範彦、吉田順子、布施谷千穂、小西郁生、塩沢丹里
    • Organizer
      第61回日本産科婦人科学会・学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] 上皮性卵巣腫瘍におけるSATB1発現の検討2009

    • Author(s)
      三橋祐布子、林晶子、堀内晶子、菊地範彦、吉田順子、布施谷千穂、塩沢丹里
    • Organizer
      第61回日本産科婦人科学会・学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] 低酸素環境卵巣癌細胞においてSlOOA4 発現はHypoxia-induciblefactor-1αを介し元進する.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
    • Related Report
      2010 Final Research Report
  • [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・学術講演会シンポジゥム 口演
    • Place of Presentation
      東京
    • Year and Date
      2008-04-14
    • Related Report
      2010 Final Research Report
  • [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・シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] 卵巣癌においてclass 1ヒストン脱アセチル化酵素(histone deacetylase, HDAC)のうちHDAC1が細胞増殖に重要である2008

    • Author(s)
      林晶子, 堀内晶子, 長田亮介, 菊地範彦, 吉田順子, 正木千穂, 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・口演
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] 低酸素環境卵巣癌細胞においてS100A4発現はHypoxia-inducible factor-1 αを介し先進する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
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-13
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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