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Felicity E B May Department of Pathology, Faculty of Medical Sciences, Northern Institute for Cancer Research and Newcastle University Institute for Ageing, University of Newcastle‐upon‐Tyne, Framlington Place, Newcastle‐upon‐Tyne NE2 4HH, UK

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Bruce R Westley Department of Pathology, Faculty of Medical Sciences, Northern Institute for Cancer Research and Newcastle University Institute for Ageing, University of Newcastle‐upon‐Tyne, Framlington Place, Newcastle‐upon‐Tyne NE2 4HH, UK

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). Adjuvant endocrine therapy for early breast cancer patients became widespread in the mid to late 1980s ( Davies et al . 2013 ). Two main categories of drugs target the dependence of malignant breast epithelial cells upon oestrogens. Aromatase inhibitors

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Yu Zhang Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China
Department of Pharmacy, Pulmonary Hospital of Wuhan, Wuhan, China
Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China

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Li Ma Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Shuguang Dong Department of Cardiology, Tongren Hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Qiaoyan Ding Department of Pharmacy, Pulmonary Hospital of Wuhan, Wuhan, China

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Shuman Wang Department of Pharmacy, Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine

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Qi Wu Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Ping Ni Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China

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Hong Zhang Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Yonggang Chen Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Jinhu Wu Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Xiong Wang Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China

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Prolactinomas have harmful effects on human health. Bromocriptine is the only commercially available drug in China, but about 25% of prolactinoma patients do not respond to it in clinic, its pathogenesis remains unknown. Thus, its pathogenesis needs to be determined to develop new therapeutic methods for prolactinomas. The expression of ERβ, TLR4, and prolactin (PRL) in the pituitary gland of C57BL/6 mice and human prolactinoma specimen was examined by immunofluorescence or immunohistochemistry. The role of TLR4 in prolactinoma was determined using estradiol-induced models of C57BL/6 wild-type and TLR4−/− mice. MMQ cells were treated with estradiol, fulvestrant, and lipopolysaccharide (LPS) or transfected with TLR4 siRNA to study the expression of ERβ, TLR4, and PRL in these cells. Furthermore, the interaction between ERβ and TLR4 was investigated by immunoprecipitation analysis. The expression of PRL and TLR4 was co-located and increased in the pituitary gland of mice and human prolactinoma specimen compared to that in the control specimen. Meanwhile, TLR4 knockout or treatment with the TLR4 inhibitor TAK242 not only significantly inhibited tumor overgrowth but also decreased the expression of PRL in estradiol-treated mice through p38 MAPK pathway regulation. However, MMQ treated with estradiol and LPS enhanced PRL expression than treated with estradiol or LPS alone. Finally, ERβ or TLR4 inhibition prevented the estradiol-induced PRL increase by regulating the TLR4/p38 MAPK pathway in vitro. Estradiol promoted prolactinoma development by activating the TLR4/p38 MAPK pathway through ERβ, and TLR4 is a potential therapeutic target for prolactinoma treatment.

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E Anderson
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A Howell
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Suzanne M Johnson MRC Molecular Endocrinology Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK

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Manijeh Maleki-Dizaji MRC Molecular Endocrinology Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK

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Jerry A Styles MRC Molecular Endocrinology Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK

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Ian N H White MRC Molecular Endocrinology Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK

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treated women ( Fisher et al. 1998 ) and has proven to be an extremely effective treatment for oestrogen receptor (ER)-positive breast cancer; however, it is not without adverse side effects. Epidemiological evidence has shown that tamoxifen

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J M W Gee
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V E Shaw
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S E Hiscox
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R A McClelland
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N K Rushmere
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R I Nicholson
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Introduction Antihormones that deplete oestrogen/oestrogen receptor α (ER) signalling comprised the first targeted therapies for breast cancer and continue to be a mainstay in the management of this disease, promoting worthwhile

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Lesley-Ann Martin
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Ian Farmer
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Stephen R D Johnston
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Simak Ali
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Mitch Dowsett
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Introduction Breast cancer is the most common cancer in women in the western world, with approximately 40 000 new cases diagnosed each year in the UK alone. Oestrogens play a pivotal role in the development of breast cancer and exert

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Alistair Ring Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Rd, London. SW3 6JJ, UK

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Mitch Dowsett Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Rd, London. SW3 6JJ, UK

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Introduction The anti-oestrogen tamoxifen is the most commonly used treatment for patients with oestrogen-receptor alpha (ER)-positive breast cancer. As an adjuvant therapy in early breast cancer tamoxifen improves overall survival

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V Craig Jordan Dallas/Ft. Worth Living Legend Chair of Cancer Research, Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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therapy that saved lives, cheaply and effectively, but also addressed whether there were any unacceptable major side effects The clinical evidence was clear: tamoxifen was only effective as an adjuvant therapy in oestrogen receptor (ER) positive breast

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Gail E de Blaquière The Medical School, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK

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Felicity E B May The Medical School, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK

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Bruce R Westley The Medical School, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK

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, Maloney et al . 2003 , Sachdev et al . 2003 , Wang et al . 2005 ) and inhibition of the receptor tyrosine kinase ( Stromberg et al . 2006 , Tazzari et al . 2007 ). In breast cancer, lifetime exposure to oestrogens is a principal risk factor

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Phungern Khongthong Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow, UK

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Antonia K Roseweir Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow, UK

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Joanne Edwards Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow, UK

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Introduction Oestrogen receptor α-positive (ER+) breast cancer constitutes more than 70% of all breast cancers ( Cardoso et al. 2012 ). Both early and metastatic disease are treated effectively with endocrine therapies, which downregulate

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