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ヒト女性乳癌における男性ホルモン、アンドロゲンの局所産生と作用機序の解明

Research Project

Project/Area Number 11F01735
Research Category

Grant-in-Aid for JSPS Fellows

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

Principal Investigator

MCNAMARA Keely (2013)  東北大学, 大学院医学系研究科, 助教

笹野 公伸 (2011-2012)  東北大学, 大学院・医学系研究科, 教授

Co-Investigator(Kenkyū-buntansha) MCNAMARA Keely  東北大学, 大学院・医学系研究科, 外国人特別研究員
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2013: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2012: ¥800,000 (Direct Cost: ¥800,000)
KeywordsAndrogen / Breast Cancer / Steroid receptors / breast cancer / androgen / Triple Negative Breast Cancer / アンドロゲン / 受容体
Research Abstract

Results of the research above revealed that AR expression in TNBC specimens correlated with lower levels of proliferation and this association was stronger in samples that also expressed enzymes for androgen synthetic pathways. This result was actually contrary to our original hypothesis, based on the research reports from others that groups characterized by very high levels of androgen receptor in the absence of estrogen receptor had a worse prognosis, and is contrary to the results of the dominate group in this area of research. The novelty of this finding was recognized by the research being awarded a prize in the presidential poster competition at the international scientific meeting ENDO2012, lead to an invitation to speak at the 15^<th> International congress on hormonal steroid and hormones & cancer in Kanazawa in 2012 and was subsequently published in the journal cancer science. Since this original contradictory finding we have been searching through possible explanations that reconcile an overall trend showing the pathological analysis reveals the androgen receptor to be a potential suppressor of proliferation, yet cell line and molecular analysis suggesting the androgen receptor as a potential oncogene. Recent data, currently under consideration for publication in the journal breast cancer research and treatment suggests that in triple negative breast cancer there may be at least two distinct types of AR expressing TNBC. In tandem with two recent reports from other groups this may provide important information in patient selection when choosing AR targeting agents as a therapy in TNBC. In addition to this, recent papers suggesting a role of ERβ in breast cancer, combined with the known overlap between androgen receptor and ERβ receptor ligands has led to an expansion of the project to investigate these factors in TNBC.

Strategy for Future Research Activity

(抄録なし)

Report

(3 results)
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (20 results)

All 2014 2013 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (11 results)

  • [Journal Article] Androgenic pathways in the progression of triple-negative breast carcinoma : a comparison between aggressive and non-aggressive subtypes2014

    • Author(s)
      McNamara, et al
    • Journal Title

      Breast Cancer Res Treat.

      Volume: 145 Issue: 2 Pages: 281-293

    • DOI

      10.1007/s10549-014-2942-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase Two Steroid Metabolism and Its Roles in Breast and Prostate Cancer Patients.2013

    • Author(s)
      McNamara, et al
    • Journal Title

      Front Endocrinol (Lausanne)

      Volume: 4 ; 4 : 116. Pages: 1-7

    • DOI

      10.3389/fendo.2013.00116

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Androgenic pathway in triple negative invasive ductal tumors : Its correlation with tumor cell proliferation.2013

    • Author(s)
      McNamara KM (18人中1人目)
    • Journal Title

      Cancer Sci.

      Volume: 104(5) Issue: 5 Pages: 639-646

    • DOI

      10.1111/cas.12121

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen receptor expression and its relevant signaling pathway in prostate cancer : a target of therapy.2013

    • Author(s)
      Nakamura Y, McNamara KM (3人中2人目)
    • Journal Title

      Curr Mol Pharmacol.

      Volume: (印刷中)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin D1 (CCND1)expression is involved in estrogen receptor beta (ERβ)in human prostate cancer.2013

    • Author(s)
      Nakamura Y, McNamara KM (8人中5番目)
    • Journal Title

      Prostate

      Volume: 73(6) Issue: 6 Pages: 590-595

    • DOI

      10.1002/pros.22599

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Androgen receptor in triple negative breast cancer.2013

    • Author(s)
      McNamara KM (6人中1人目)
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 133 Pages: 66-76

    • DOI

      10.1016/j.jsbmb.2012.08.007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostate epithelial AR inactivation leads to increased intraprostatic androgen synthesis.2013

    • Author(s)
      McNamara KM (5人中1人目)
    • Journal Title

      Prostate

      Volume: 15;73(3) Issue: 3 Pages: 316-327

    • DOI

      10.1002/pros.22570

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen-related receptor α in normal adrenal cortex and adrenocortical tumors : involvement in development and oncogenesis.2013

    • Author(s)
      Felizola SJ, McNamara KM (10人中6人目)
    • Journal Title

      Mol Cell Endocrinol.

      Volume: 30;365(2) Issue: 2 Pages: 207-211

    • DOI

      10.1016/j.mce.2012.10.020

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients.2012

    • Author(s)
      Tamaki K, McNamara KM (13人中11人目)
    • Journal Title

      Breast Cancer.

      Volume: (印刷中)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Estrogenic pathways exist in TNBC and correlate with androgen receptor status2013

    • Author(s)
      McNamara, et al
    • Organizer
      San Antonio Breast Cancer Symposium 2013
    • Place of Presentation
      San Antonio アメリカ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Clinicopathological significance of Androgen Receptor status in recurrent triple negative breast carcinoma patients2013

    • Author(s)
      McNamara, et al
    • Organizer
      Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lack of AR is associated with an increase in Ki-67 labelling index in triple negative ductal carcinoma in situ.2013

    • Author(s)
      McNamara, et al
    • Organizer
      Endocrine Society of Australia
    • Place of Presentation
      Sydney オーストラリア
    • Related Report
      2013 Annual Research Report
  • [Presentation] A comparison of an androgenic pathway between development and reoccurrence/progression of triple negative breast cancer patients2013

    • Author(s)
      McNamara, et al
    • Organizer
      ENDO2013
    • Place of Presentation
      San Francisco アメリカ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Androgen receptor in triple negative breast cancer2012

    • Author(s)
      McNamara Keely
    • Organizer
      15^<th> International congress on hormonal steroid and hormones & cancer
    • Place of Presentation
      金沢(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Androgen receptor in invasive ductal carcinoma and ductal carcinoma in situ (DCIS)component in triple negative breast cancer(TNBC) patients2012

    • Author(s)
      McNamara Keely
    • Organizer
      15^<th> International congress on hormonal steroid and hormones & cancer
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] Activation of androgenic pathways results in lower tumor cell proliferation in triple negative breast cancer2012

    • Author(s)
      McNamara Keely
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] Intratumoral androgen production and actions in Triple Negative Breast Cancer-correlation with tumor cell proliferation and clinical outcome2012

    • Author(s)
      McNamara Keely
    • Organizer
      ESA 2012
    • Place of Presentation
      Gold Coast, Australia
    • Related Report
      2012 Annual Research Report
  • [Presentation] Co-Expression of Androgen Receptor and 5aR1 in Triple-Negative Breast Cancer (TNBC)IS Associated with Lower Rates of Tumor Cell Proliferation(SAT261)2012

    • Author(s)
      McNamara Keely
    • Organizer
      ENDO 2012
    • Place of Presentation
      Huston Texas USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] 5αR2 expression in PIN like lesions of the PEARKO mouse mimics 5αR2 expression in human PIN2011

    • Author(s)
      McNamara K, Nakamura Y, Handelsman DJ, Sasano H, Simanainen U
    • Organizer
      第29回内分泌代謝学サマーセミナー
    • Place of Presentation
      仙台市
    • Year and Date
      2011-07-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Unbalanced AR signaling in the PEARKO (prostate epithelial AR knock-out) mouse : a model of early stage human prostate malignancy2011

    • Author(s)
      Keely McNamara
    • Organizer
      第29回内分泌代謝学サマーセミナー
    • Place of Presentation
      仙台市
    • Year and Date
      2011-07-07
    • Related Report
      2011 Annual Research Report

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Published: 2013-04-25   Modified: 2024-03-26  

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