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ヒト骨肉腫はエストロゲンを産生するか?

Research Project

Project/Area Number 20659053
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionTohoku University

Principal Investigator

笹野 公伸  Tohoku University, 大学院・医学系研究科, 教授 (50187142)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2009: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2008: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords骨 / 骨肉腫 / 骨芽細胞 / aryl hydrocarbon receptor / エストロゲン / アロマターゼ / 肉腫 / 性ステロイド / プロゲステロン / アンドロゲン / ホルモン
Research Abstract

前回我々はestrogenic compounds(bisphenol A)のSteroid and xenobiotic receptorを介した作用を報告した。今回、SXRと同様にcytochrome P450の制御に関わるaryl hydrocarbon receptor(AhR)に注目し、正常骨組織から骨肉腫までの作用について検討を行った。免疫組織化学の結果、正常骨組織ではAhRは骨芽細胞に発現することが明らかとなった。また、骨芽細胞の培養細胞(hFOB)を用いたマイクロアレイ解析(human 1A : Agilent Technologies)ではestrogen receptor beta(ERbeta)、エストロゲン合成酵素であるアロマターゼ、エストロゲン代謝酵素であるCYP1Bの制御に関わることが明らかとなった。骨肉腫培養細胞株MG-63およびhFOBを用いた定最的PCRにおいても、AhRリガンドである3-methylcholanthreneの添加によってERbeta、アロマターゼ、CYP1Bの発現増加を認めた。以上のことから、AhRは骨芽細胞においてエストロゲン作用の調節に関与することが示唆された。一方、ヒト骨肉腫組織を用いた免疫組織化学では、骨肉腫組織にBRbetaが発現することを確認したが、アロマターゼの発現は認められなかった。このことから正常骨細胞と癌細胞においては、AhRの性質、特に応答遺伝子の発現パターンが大きく異なり、エストロゲンシグナルを介した骨肉腫の病体と関連することが示唆された。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (34 results)

All 2010 2009 2008

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (14 results)

  • [Journal Article] Highly concordant coexpression of aromatase and estrogen receptor beta in non-small cell lung cancer.2010

    • Author(s)
      Abe K, Miki Y, Ono K, Mori M, Kakinuma H, Kou Y, Kudo N, Koguchi M, Niikawa H, Suzuki S, Evans DB, Sugawara S, Suzuki T, Sasano H.
    • Journal Title

      Hum Pathol. 41

      Pages: 190-198

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aromatase and in situ estrogen production in DCIS (ductal carcinoma in situ) of human breast.2010

    • Author(s)
      Sasano H, Miki Y, Shibuya R, Suzuki T.
    • Journal Title

      J Steroid Biochem Mol Biol. 118

      Pages: 242-245

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Breast cancer aromatase expression evaluated by the novel antibody 677 : Correlations to intra-tumor estrogen levels and hormone receptor status.2010

    • Author(s)
      Geisler J, Suzuki T, Helle H, Miki Y, Nagasaki S, Duong NK, Ekse D, Aas T, Evans DB, Lonning PE, Sasano H.
    • Journal Title

      J Steroid Biochem Mol Biol. 118

      Pages: 237-241

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epitope characterization of an aromatase monoclonal antibody suitable for the assessment of intratumoral aromatase activity.2009

    • Author(s)
      Hong Y, Li H, Ye J, Miki Y, Yuan YC, Sasano H, Evans DB, Chen S.
    • Journal Title

      PLoS One 4

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In situ estrogen production and its regulation in human breast carcinoma : from endocrinology to intracrinology.2009

    • Author(s)
      Sasano H, Miki Y, Nagasaki S, Suzuki T.
    • Journal Title

      Pathol Int 59

      Pages: 777-789

    • NAID

      10027382046

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Steroid hormones are produced at the sites of action.2009

    • Author(s)
      Sasano H.
    • Journal Title

      Endocr J 56

      Pages: 825-826

    • NAID

      10026915077

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of 17beta-hydroxysteroid dehydrogenase type 12 by SREBP-1.2009

    • Author(s)
      Nagasaki S, Miki Y, Akahira J, Suzuki T, Sasano H.
    • Journal Title

      Mol Cell Endocrinol 307

      Pages: 163-168

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The mediator complex subunit 1 enhances transcription of genes needed for adrenal androgen production.2009

    • Author(s)
      Nakamura Y, Xing Y, Sasano H, Rainey WE.
    • Journal Title

      Endocrinology 150

      Pages: 4145-4153

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 17beta-hydroxysteroid dehydrogenase type 11 (Pan1b) expression in human prostate cancer.2009

    • Author(s)
      Nakamura Y, Suzuki T, Arai Y, Sasano H.
    • Journal Title

      Neoplasma 56

      Pages: 317-320

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro : estrogen receptor dependent or independent pathways of raloxifene.2009

    • Author(s)
      Miki Y, Suzuki T, Nagasaki S, Hata S, Akahira J, Sasano H.
    • Journal Title

      J Steroid Biochem Mol Biol 113

      Pages: 281-289

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 17beta-hydroxysteroid dehydrogenases in human breast cancer.2009

    • Author(s)
      Nagasaki S, Miki Y, Akahira J, Suzuki T, Sasano H.
    • Journal Title

      Ann N Y Acad Sci 1155

      Pages: 25-32

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 17Beta-hydroxysteroid dehydrogenase type 12 in human breast carcinoma : a prognostic factor via potential regulation of fatty acid synthesis2009

    • Author(s)
      Nagasaki S, Suzuki T, Miki Y, Akahira J, Kitada K, Ishida T, Handa H, Ohuchi N, Sasano H.
    • Journal Title

      Cancer Res 69

      Pages: 1392-1399

    • Related Report
      2009 Annual Research Report 2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aromatase expression and outcomes in the P024 neoadjuvant endocrine therapy trial2009

    • Author(s)
      Ellis MJ, Miller WR, Tao Y, Evans DB, Chaudri Ross HA, Miki Y, Suzuki T, Sasano H.
    • Journal Title

      Breast Cancer Res Treat (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chicken ovalbumin upstream promoter transcription factor II in human breast carcinoma : Possible regulator of lymphangiogenesisvia vascular endothelial growth factor-C expression2009

    • Author(s)
      Nagasaki S, Suzuki T, Miki Y, Akahira JI, Shibata H, Ishida T, Ohuchi N, Sasano H.
    • Journal Title

      Cancer Sci (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DAX-1A(NROB1A)Expression Levels are Extremely Low Compared to DAX-1(NROBI)in Human Steroidogenic Tissues2009

    • Author(s)
      Nakamura Y, Vargas Morris C, Sasano H, Rainey WE.
    • Journal Title

      Horm Metab Res 41

      Pages: 30-34

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear Receptor DAX1 in Human Prostate Cancer : A Novel Independent Biological Modulator2009

    • Author(s)
      Nakamura Y, Suzuki T, Arai Y, Sasano H.
    • Journal Title

      Endocr J 56

      Pages: 39-44

    • NAID

      10025610118

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Steroid Sulfatase and Estrogen Sulfotransferase in Colon Carci coma : Regulators of Intratumoral Estrogen Concentrations and Potent Prognostic Factors2009

    • Author(s)
      Sato R, Suzuki T, Katayose Y, Miura K, Shiiba K, Tateno H, Miki Y, Akahira J, Kamogawa Y, Nagasaki S, Yamamoto K, Ii T, Egawa S, Evans DB, Unno M, Sasano H.
    • Journal Title

      Cancer Res 69

      Pages: 914-922

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 17beta-hydroxysteroid dehydrogenases in human breast cancer2009

    • Author(s)
      Nagasaki S, Miki Y, Akahira T. Suzuki T. Sasano H.
    • Journal Title

      Ann N Y Acad Sci 1155

      Pages: 25-32

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New developments in intracrinology of human breast cancer : estrogen sulfatase and sulfotransferase2009

    • Author(s)
      Sasano H, Nagasaki S, Miki Y, Suzuki T.
    • Journal Title

      Ann N Y Acad Sci 1155

      Pages: 76-79

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of estrogen receptor beta isoform expression and its corr elation with aberrant DNA methylation of the 5'-untranslated region in human epithelial ovarian carcinoma2008

    • Author(s)
      Suzuki F, Akahira J, Miura I, Suzuki T, Ito K, Hayashi S, Sasano H, Yaegashi N.
    • Journal Title

      Cancer Sci 99

      Pages: 2365-2372

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Increased estrogen sulfatase (STS) and 17ss-hydroxysteroid dehydrogenase type1 (17ss-HSD1) after neoadjuvant aromatase inhibitor therapy in breast cancer patients2010

    • Author(s)
      N Chanplakorn, P Chanplakorn, K Ono, Y Miki, S Saji, T Ueno, M Toi, 笹野公伸
    • Organizer
      6th Annual Conference of OOTR
    • Place of Presentation
      ウェスティン都ホテル京都(京都府)
    • Year and Date
      2010-02-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] 10%ホルマリン固定パラフィン包埋標本から抽出したTotalRNAおよびmicroRNAの質的検討2009

    • Author(s)
      三浦伊久美、三木康宏、赤平純一、鈴木貴、笹野公伸
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2009-05-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Controversies in Endocrine Treatment : Effective utilization of steroidal and non-steroidal aromatase inhibitors-Now and in the Future.2009

    • Author(s)
      笹野公伸
    • Organizer
      Taiwan Aromatase Conference
    • Place of Presentation
      NTUH International Convention Center(Taiwan)
    • Year and Date
      2009-04-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] Gene Profiling and histopathological analysis in early breast carcinoma-advantages and limitations2009

    • Author(s)
      笹野公伸
    • Organizer
      Kyoto Breast Cancer Consensus Conference 2009
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2009-04-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Intratumoral estrogen production in human breast cancer-Its regulation and inhibition2009

    • Author(s)
      笹野公伸
    • Organizer
      The Endocrine Society of Australia 52nd Annual Scientific Meeting
    • Place of Presentation
      Adelaide Convention Center(Australia)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Intracrinology of Estorogen and Androgens in Human Breast Care inoma2008

    • Author(s)
      H Sasano, Y Miki, S Nagasaki, T Suzuki
    • Organizer
      13^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Quebec Hilton (Canada)
    • Year and Date
      2008-09-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] Comparative Effects of Raloxifene,Tamoxifen and Estradiol on Human Osteoblast In Vitro2008

    • Author(s)
      Y Miki, S Nagasaki, S Hata, J-I Akahira, T Suzuki, H Sasano
    • Organizer
      The Endocrine Society's 90th Annual Meeting
    • Place of Presentation
      San Francisco Convention Center(USA)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Gene Profiling of the Reticularis and Fasciculata Zones of Hum an Adult Adrenals2008

    • Author(s)
      Y Nakamura, PJ Hornsby, PR Casson, R Morimoto, F Satoh H Sasano, WE Rainey
    • Organizer
      The Endocrine Society's 90th Annual Meeting
    • Place of Presentation
      San Francisco Convention Center(USA)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Does DAX1A(NROBIA)Play a Role in Adrenal Function?2008

    • Author(s)
      Y Nakamura, CV Morris, H Sasano, WE Rainey
    • Organizer
      The Endocrine Society's 90th Annual Meeting
    • Place of Presentation
      San Francisco Convention Center(USA)
    • Related Report
      2008 Annual Research Report
  • [Presentation] The Expression of steroid sulfatase and Estrogen Sulfotransferase In Human Epithelial Ovarian Cancer2008

    • Author(s)
      J-I Akahira, T Suzuki, F Suzuki, I Miura, Y Miki, K Ito, N Yaegashi, H Sasano
    • Organizer
      The Endocrine Society's 90th Annual Meeting
    • Place of Presentation
      San Francisco Convention Center(USA)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Intracrinology of sex-steroids in ductal carcinoma In situ(DCIS)of the breast : comparison to invasive Ductal carcinoma(IDC)and non-neoplastic breas2008

    • Author(s)
      H Sasano, Y Miki, R Shibuya, I Suzuki
    • Organizer
      18th International symposium of the journal of steroid Biochemistry and molecular biology
    • Place of Presentation
      Conference Center -Seefeld (Austria)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Proliferative effect of estrogen on human lung cancer in vitro -Aromatase as a possible target for human lung cancer therapy-2008

    • Author(s)
      Y Miki, H Niikawa, K Abe, S Suzuki, S Hata, J Akahira, T Suzuki, H Sasano
    • Organizer
      13^<th> International Congress on Hormonal Ster oids and Hormones & Cancer
    • Place of Presentation
      Quebec Hilton (Canada)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Immunolocalization of COUP-TF in human breast carcinoma : a possible prognostic factor2008

    • Author(s)
      S Nagasaki, T Suzuki, Y Miki,.T Akahira. H Sasano
    • Organizer
      13^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Quebec Hilton (Canada)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Aromatase and in situ estrogen production in DCIS(ductal carcinoma in situ) of human breast2008

    • Author(s)
      H Sasano, Y Miki, R Shibuya, T Suzuki
    • Organizer
      Ninth International Aromatase Conference
    • Place of Presentation
      Shanghai(China)
    • Related Report
      2008 Annual Research Report

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

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