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Eva Baxter Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

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Karolina Windloch Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

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Greg Kelly Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

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Jason S Lee Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

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Frank Gannon Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

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Donal J Brennan UCD School of Medicine, Catherine McAuley Research Centre, Mater Misericordiae University Hospital, Dublin, Ireland
Cancer Biology and Therapeutics Laboratory, UCD Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland
Systems Biology Ireland, University College Dublin, Belfield, Dublin, Ireland

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Introduction Over 1000 oestrogen-responsive genes have been identified in vitro , predominantly using the luminal breast cancer cell line MCF7, and these are involved in a variety of processes such as the cell cycle, proliferation and

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Ninu Poulose Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK

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Ian G Mills Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK
Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK

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Rebecca E Steele Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK

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). The prostate is also a target for oestrogens among which oestradiol-17β is considered the most potent inducer of prostatic proliferation and promotes epithelial-to-mesenchymal transition in benign prostatic epithelial cells ( Shi et al . 2017

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Anthony Howell CRUK Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK

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Background The critical role played by oestrogen in breast cancer has driven a huge amount of research into the development of hormonal therapies that are able to block oestrogen-mediated cell signalling. For more than 30 years

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

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

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Introduction The tissues of the female reproductive tract (vagina, cervix, uterus and fallopian tube) are key targets for the action of oestrogens by virtue of their expression of oestrogen receptors (ERs). During a woman's reproductive years, these

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Cindy M Staka Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, UK

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Robert I Nicholson Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, UK

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Julia M W Gee Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, UK

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Introduction Oestrogen deprivation, achieved clinically in post-menopausal women using aromatase inhibitors or in premenopausal women using ovarian ablation or suppression with luteinizing hormone-releasing hormone superagonists, is

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Akiko Ebata Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan
Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Takashi Suzuki Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Kiyoshi Takagi Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Yasuhiro Miki Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Yoshiaki Onodera Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Yasuhiro Nakamura Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Fumiyoshi Fujishima Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Kazuyuki Ishida Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Mika Watanabe Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Kentaro Tamaki Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan
Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Takanori Ishida Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Noriaki Ohuchi Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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Hironobu Sasano Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan
Departments of, Pathology, Surgical Oncology, Pathology and Histotechnology, Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan

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to identify the possible molecular mechanisms related to the acquisition of invasive properties and subsequently to improve clinical outcome of early breast cancer patients. It is well known that oestrogens play important roles in the progression of

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Debbie Clements
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Sarah L Asprey
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Thomas A McCulloch Division of Therapeutics and Molecular Medicine, Department of Histopathology, Academic Unit of Cancer Studies, D Floor, South Block, University Hospital, University of Nottingham, Nottingham NG7 2UH, UK

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Theresa A Morris Division of Therapeutics and Molecular Medicine, Department of Histopathology, Academic Unit of Cancer Studies, D Floor, South Block, University Hospital, University of Nottingham, Nottingham NG7 2UH, UK

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Susan A Watson Division of Therapeutics and Molecular Medicine, Department of Histopathology, Academic Unit of Cancer Studies, D Floor, South Block, University Hospital, University of Nottingham, Nottingham NG7 2UH, UK

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Simon R Johnson
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cellular kinase governing proliferation and apoptosis ( Li et al . 2004 ). Although TSC occurs equally in men and women, angiomyolipoma is more common and larger in women and is thought to be oestrogen dependent. LAM also occurs almost exclusively in women

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G P Risbridger Monash Institute of Reproduction and Development (Centre for Urological Research), Monash University, Melbourne, Victoria, Australia. gail.risbridger@med.monash.edu.au

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J J Bianco Monash Institute of Reproduction and Development (Centre for Urological Research), Monash University, Melbourne, Victoria, Australia. gail.risbridger@med.monash.edu.au

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S J Ellem Monash Institute of Reproduction and Development (Centre for Urological Research), Monash University, Melbourne, Victoria, Australia. gail.risbridger@med.monash.edu.au

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S J McPherson Monash Institute of Reproduction and Development (Centre for Urological Research), Monash University, Melbourne, Victoria, Australia. gail.risbridger@med.monash.edu.au

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Androgens are essential for stimulating normal development, growth and secretory activities of the prostate whereas oestrogens are generally regarded as inhibitors of growth. Evidence for the local synthesis of oestrogens includes the detection of aromatase mRNA and protein in the stroma of human non-malignant tissues and in malignant tissue, where it is detected in epithelial tumour cells. As well, aromatase activity was measured by biochemical assay and protein was detected in prostatic non-malignant and tumour cell lines. Taken together with the identification of direct oestrogenic actions on the prostate, these results suggest that alterations in local oestrogen synthesis may have significant consequences in malignancy of these organs. Genetically modified mouse models were studied in order to evaluate the action of oestrogens alone or in combination with androgens on the prostate gland. Hypogonadal (hpg) mice are deficient in gonadotrophins and androgens but showed direct proliferative responses to oestradiol. The responses were characterised by discrete lobe-specific changes including smooth-muscle regression, fibroblast proliferation, inflammation, and basal epithelial cell proliferation and metaplasia. The aromatase knockout (ArKO) mouse, deficient in oestrogens due to a non-functional aromatase enzyme, developed prostatic hyperplasia during the lifelong exposure to elevated androgens, however, no malignant changes were detected in the prostate at any time. In contrast, combined androgen and oestrogen treatment has been shown to induce prostatic dysplasia and adenocarcinoma. These results demonstrate that malignant changes to the prostate gland are dependent upon both androgenic and oestrogenic responses and that neither hormone alone is sufficient to evoke aberrant patterns of growth, resulting in malignancy.

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Balaji Ramachandran Department of Molecular Oncology, Cancer Institute (W.I.A.), Adyar, Chennai, India

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recognised to be highly influenced by oestrogen hormones that control proliferation, apoptosis, migration and metastasis ( King 1991 , Henderson & Feigelson 2000 , Ramachandran et al . 2011 ). The uterine cervix is also a part of the female reproductive

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Edward B Alabraba
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Philippe Taniere Liver Research Group, Department of Pathology,, Endocrine Research Group,, Liver Unit,, University of Birmingham, Birmingham B15 2TT, UK

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Gary M Reynolds
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Paul M Stewart Liver Research Group, Department of Pathology,, Endocrine Research Group,, Liver Unit,, University of Birmingham, Birmingham B15 2TT, UK

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Stephen J Wigmore
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Simon R Bramhall Liver Research Group, Department of Pathology,, Endocrine Research Group,, Liver Unit,, University of Birmingham, Birmingham B15 2TT, UK

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confined to endocrine pancreas tissue ( Doglioni et al . 1990 , Viale et al . 1992 ). A decade ago, oestrogen receptor (ER) presence was demonstrated in pancreatic tumour tissue using radioligand binding assays and Scatchard analysis ( Greenway et al

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