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Douglas A Gibson MRC Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

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Ioannis Simitsidellis MRC Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

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Frances Collins MRC Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

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Philippa T K Saunders MRC Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

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Introduction Endometrial cancer (EC) and ovarian cancer are common gynaecological malignancies; however, the impact of androgen action in these cancers is poorly understood. Epidemiological evidence suggests that androgens may be important in the

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Tianzhu Zang Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Mary-Ellen Taplin Harvard Medical School, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Daniel Tamae Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Wanling Xie Department of Biostatistics and Computational Biology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Clementina Mesaros Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Department of Systems Pharmacology & Translational Therapeutics, Center for Cancer Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Zhenwei Zhang Department of Biostatistics and Computational Biology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Glenn Bubley Beth Israel Deaconess Medical Center, Genitourinary Medical Oncology, Boston, Massachusetts, USA

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Bruce Montgomery Department of Medicine, University of Washington, Seattle, Washington, USA

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Steven P Balk Beth Israel Deaconess Medical Center, Genitourinary Medical Oncology, Boston, Massachusetts, USA

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Elahe A Mostaghel Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

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Ian A Blair Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Department of Systems Pharmacology & Translational Therapeutics, Center for Cancer Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Trevor M Penning Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Department of Systems Pharmacology & Translational Therapeutics, Center for Cancer Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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alleviate the symptoms of patients with advanced or metastatic CaP, the disease is recognized as being androgen dependent ( Huggins & Hodges 2002 , Perlmutter & Lepor 2007 , Shafi et al . 2013 , Wong et al . 2014 ). In males, the production of potent

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Matias Knuuttila Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, Turku, Finland

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Arfa Mehmood Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

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Jenni Mäki-Jouppila Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, Turku, Finland

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Henrik Ryberg Center for Bone and Arthitis Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Pekka Taimen Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland

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Juha Knaapila Department of Urology, Turku University Hospital, Turku, Finland

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Otto Ettala Department of Urology, Turku University Hospital, Turku, Finland

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Peter J Boström Department of Urology, Turku University Hospital, Turku, Finland

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Claes Ohlsson Center for Bone and Arthitis Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Mikko S Venäläinen Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

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Asta Laiho Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

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Laura L Elo Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

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Petra Sipilä Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, Turku, Finland

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Sari I Mäkelä Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, Turku, Finland
Functional Foods Forum, University of Turku, Turku, Finland

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Matti Poutanen Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, Turku, Finland
Center for Bone and Arthitis Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Introduction Androgens play a crucial role in the normal development and growth of the prostate and the growth of prostate cancer. The prostate tissue is known for the local biosynthesis of dihydrotestosterone (DHT), which is the principal

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Kiyoshi Ito Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDeS), Tohoku University, Sendai, Japan
Department of Disaster Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Yasuhiro Miki Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDeS), Tohoku University, Sendai, Japan

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Takashi Suzuki Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Keely May McNamara Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Hironobu Sasano Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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carcinoma especially that of the endometrioid type, also known as type I endometrial carcinoma ( Bokhman 1983 ). However, in contrast to studies regarding estrogens, the possible impact of androgen actions on endometrial carcinoma has largely remained

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Nicholas Russell Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia

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Ada Cheung Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia

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Mathis Grossmann Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia

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. Androgen deprivation therapy (ADT) has been a cornerstone of PCa management since the 1940s. A variety of approaches have been used: bilateral orchiectomy; high-dose oral or parenteral estrogens; luteinizing hormone-releasing hormone (LHRH) agonists (LHRHa

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Keely M McNamara
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Nicole L Moore Department of Pathology Tohoku University School of Medicine, Miyagi, Sendai, Japan

Dame Roma Mitchell Cancer Research Laboratories Discipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia

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Theresa E Hickey Department of Pathology Tohoku University School of Medicine, Miyagi, Sendai, Japan

Dame Roma Mitchell Cancer Research Laboratories Discipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia

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Hironobu Sasano
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Wayne D Tilley Department of Pathology Tohoku University School of Medicine, Miyagi, Sendai, Japan

Dame Roma Mitchell Cancer Research Laboratories Discipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia

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cancer therapies between the 1940s and the 1980s. Although this therapeutic strategy displayed sound clinical efficacy ( Tormey et al . 1983 , Ingle et al . 1991 ), the use of androgen-based hormonal therapies fell from favour due to their

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Stefan J Barfeld Prostate Cancer Research Group Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway

Department of Cancer Prevention Institute of Cancer Research

Department of Urology Oslo University Hospital, N-0424 Oslo, Norway

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Harri M Itkonen Prostate Cancer Research Group Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway

Department of Cancer Prevention Institute of Cancer Research

Department of Urology Oslo University Hospital, N-0424 Oslo, Norway

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Alfonso Urbanucci Prostate Cancer Research Group Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway

Department of Cancer Prevention Institute of Cancer Research

Department of Urology Oslo University Hospital, N-0424 Oslo, Norway

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Ian G Mills Prostate Cancer Research Group Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway

Department of Cancer Prevention Institute of Cancer Research

Department of Urology Oslo University Hospital, N-0424 Oslo, Norway
Prostate Cancer Research Group Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway

Department of Cancer Prevention Institute of Cancer Research

Department of Urology Oslo University Hospital, N-0424 Oslo, Norway
Prostate Cancer Research Group Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway

Department of Cancer Prevention Institute of Cancer Research

Department of Urology Oslo University Hospital, N-0424 Oslo, Norway

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responsible for secreting factors that enhance sperm viability during reproduction. Both the development of the prostate gland and maintenance of these secretory functions require androgens and the androgen receptor (AR; Pritchard & Nelson 2008 ). While the

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Garrett Daniels Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Yirong Li Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Lan Lin Gellert Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Albert Zhou Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Jonathan Melamed Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Xinyu Wu Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Xinming Zhang Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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David Zhang Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Daniel Meruelo Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA
Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Susan K Logan Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA
Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA
Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Ross Basch Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Peng Lee Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA
Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA
Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA
Department of Pathology, Department of Pathology, NYU Cancer Institute, Department of Urology, Department of Pharmacology, New York Harbor Healthcare System, New York University School of Medicine, New York, New York, USA

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Introduction It has long been known that androgens are critical in the growth and progression of prostate cancer ( Dehm & Tindall 2006 ). Androgens signal through the androgen receptor (AR), a member of the steroid receptor family of transcription

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D Alwyn Dart
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Bradley Spencer-Dene Androgen Signalling Laboratory, Department of Histopathology, Department of Oncology, Imperial College London, Du Cane Road, London W12 0NN, UK

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Simon C Gamble
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Jonathan Waxman
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Charlotte L Bevan
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. 2007 , Jemal et al . 2008 ). The androgen signalling pathway is central in prostate cancer progression and therapy, as tumours are initially dependent upon androgens for growth ( Agoulnik & Weigel 2006 ). The principal circulating androgen is

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Amina Zoubeidi Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada

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Paramita M Ghosh Department of Urologic Surgery, School of Medicine, University of California Davis, Sacramento, California, USA
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, California, USA
Department of Veterans Affairs, Northern California Health Care System, Mather, California, USA

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understanding has evolved from the observation that androgen withdrawal, either surgical or pharmacological, resulted in prostatic atrophy in animal models, to its application in patients, to the investigation of the mysterious way in which prostate cancer

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