Circulating oestrogen receptor mutations and splice variants in advanced prostate cancer

Qu, Liang G.; Wardan, Hady; Davis, Ian D.; Iddawela, Mahesh; Sluka, Pavel; Pezaro, Carmel

doi:10.1111/bju.14797

Cited by 11 publications

(13 citation statements)

References 35 publications

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“…Markedly reduced ERβ levels can be observed in grade 4/5 carcinomas compared to that in grade 3 carcinomas ( 186 ). Five splice variants of ERα and ERβ (ERα-36, ERβ2, ERβ3, ERβ4, and ERβ5) were detected in men with and without prostate cancer ( 187 ). However, the role of ERα-36 remains unclear.…”

Section: Ers In the Manifestation Of Diseasesmentioning

confidence: 99%

Role of estrogen receptors in health and disease

Chen

Ouyang

2022

Front. Endocrinol.

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Estrogen receptors (ERs) regulate multiple complex physiological processes in humans. Abnormal ER signaling may result in various disorders, including reproductive system-related disorders (endometriosis, and breast, ovarian, and prostate cancer), bone-related abnormalities, lung cancer, cardiovascular disease, gastrointestinal disease, urogenital tract disease, neurodegenerative disorders, and cutaneous melanoma. ER alpha (ERα), ER beta (ERβ), and novel G-protein-coupled estrogen receptor 1 (GPER1) have been identified as the most prominent ERs. This review provides an overview of ERα, ERβ, and GPER1, as well as their functions in health and disease. Furthermore, the potential clinical applications and challenges are discussed.

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Section: Ers In the Manifestation Of Diseasesmentioning

confidence: 99%

Role of estrogen receptors in health and disease

Chen

Ouyang

2022

Front. Endocrinol.

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“…Recently, Qu et al characterized circulating estrogen receptor mutants and isoforms in men from blood-derived RNA samples that were sequentially characterized from healthy and advanced PCa patients. The authors found six ERα mutations (E380Q, L536Q, Y537C, Y537S, Y537N, and D538G) in plasma from patients with advanced PCa, and six ERα and ERβ isoforms (ERα-66, ERα-36, ERβ1, ERβ2, ERβ4, and ERβ5) ( 19 ).…”

Section: Splice Variants In the Estrogen Receptormentioning

confidence: 99%

Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms

et al. 2022

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Estrogens are hormones that have been extensively presented in many types of cancer such as breast, uterus, colorectal, prostate, and others, due to dynamically integrated signaling cascades that coordinate cellular growth, differentiation, and death which can be potentially new therapeutic targets. Despite the historical use of estrogens in the pathogenesis of prostate cancer (PCa), their biological effect is not well known, nor their role in carcinogenesis or the mechanisms used to carry their therapeutic effects of neoplastic in prostate transformation. The expression and regulation of the estrogen receptors (ERs) ERα, ERβ, and GPER stimulated by agonists and antagonists, and related to prostate cancer cells are herein reviewed. Subsequently, the structures of the ERs and their splice variants, the binding of ligands to ERs, and the effect on PCa are provided. Finally, we also assessed the contribution of molecular simulation which can help us to search and predict potential estrogenic activities.

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“…Alternative splicing of ER-mRNAs leads to the existence of several splice variants of ERβ, which have different roles but are structurally similar ( Figure 1 ) [ 17 ]. For example, it has been suggested that ERβ splice variants are associated with biological behaviors such as drug resistance and apoptosis in prostate cancer [ 18 , 19 ]. Faria et al found that, in prostate cancer, ERβ2 and ERβ can induce stem cell properties of tumors as well as the development of chemoresistance.…”

Section: The Structure Of Estrogen Receptorsβ (Erβ)mentioning

confidence: 99%

Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

Liu

Jiang

2022

Med Sci Monit

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Prostate cancer remains the most prevalent cancer among men worldwide; however, as a sex hormone-dependent cancer, sex hormones and their receptor signaling play an important role in the development and progression of cancer. Most current treatment options for prostate cancer thus revolve around the inhibition of androgen signaling (eg, ADT), which, although effective in the early stages, eventually progresses to treatment-resistant prostate cancer with no effective follow-up options. Recent studies have shown that among the nuclear receptor family members, in addition to androgen receptors, estrogen receptor (ER) plays an important biological function as a transcription factor and regulatory protein in various cancers, acting either directly or indirectly by forming homodimers or heterodimers with ligands. In this paper, we review the application of ERβ in animal models and in vitro experiments in the last 5 years, as well as the presence and role of some of its splice variants. We summarize the overview and update of ERβ in prostate cancer, and provide a corresponding analysis of some current research disagreements. Its crosstalk action on some important cancer growth-related signaling pathways (eg, TGF-β and ERK), regulation of downstream target proteins (eg, nuclear translocation of EGFR and expression of oncogenic-related protein MMP-2), and interactions with related ERβ co-regulators (eg, ZFHX3), agonists, and antagonists in prostate cancer are highlighted, and the resulting effects on tumor progression are described. In addition, the paper describes its current potential clinical application as a novel therapeutic strategy and some of the challenges it faces.

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Circulating oestrogen receptor mutations and splice variants in advanced prostate cancer

Cited by 11 publications

References 35 publications

Role of estrogen receptors in health and disease

Role of estrogen receptors in health and disease

Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms

Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

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