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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
Department of Pharmacy, Pulmonary Hospital of Wuhan, Wuhan, China
Faculty of Pharmacy, Hubei University of Chinese Medicine, 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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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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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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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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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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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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, 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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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
