An overview on Estrogen receptors signaling and its ligands in breast cancer

Khan, Muhammad Zafar; Uzair, Muhammad; Nazli, Adila; Chen, Jianzhong

doi:10.1016/j.ejmech.2022.114658

Cited by 48 publications

(31 citation statements)

References 187 publications

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“…The second way by which estrogen elicits its effects is through a non-genomic mechanism. In this mechanism, the ligand–ER dimer can locate itself in the cytoplasm or at the membrane, eventually activating the downstream protein kinases and phosphatases ( 42 ).…”

Section: Downstream Signaling Pathways Of Estrogenmentioning

confidence: 99%

Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex

Zhong¹,

Sun²,

Lü³

et al. 2023

Front. Immunol.

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Although estrogen is predominantly related to the maintenance of reproductive functioning in females, it mediates various physiological effects in nearly all tissues, especially the central nervous system. Clinical trials have revealed that estrogen, especially 17β-estradiol, can attenuate cerebral damage caused by an ischemic stroke. One mechanism underlying this effect of 17β-estradiol is by modulating the responses of immune cells, indicating its utility as a novel therapeutic strategy for ischemic stroke. The present review summarizes the effect of sex on ischemic stroke progression, the role of estrogen as an immunomodulator in immune reactions, and the potential clinical value of estrogen replacement therapy. The data presented here will help better understand the immunomodulatory function of estrogen and may provide a basis for its novel therapeutic use in ischemic stroke.

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Section: Downstream Signaling Pathways Of Estrogenmentioning

confidence: 99%

Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex

Zhong¹,

Sun²,

Lü³

et al. 2023

Front. Immunol.

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“…Breast cancer (BC) has become the most common cancer worldwide in 2020 with an incidence rate of 11.7%, of which the estrogen receptor-positive (ER + ) subtype accounts for 79%. , ER, including ERα and ERβ, plays a crucial part in the expression of target genes through signal transduction and transcription factor. , Thousands of representative ER target genes have been demonstrated to impinge on breast carcinogenesis. As a transcription factor for genes associated with tumor cell proliferation and growth, ERα is overexpressed in ER + BC and is the main cause for the formation and development of ER + BC, so it is recognized as the most important therapeutic target for curing ER + BC …”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Dual-Target Estrogen Receptor α Degraders with Tubulin Inhibitory Activity for the Treatment of Endocrine-Resistant Breast Cancer

Deng

Ning

et al. 2023

J. Med. Chem.

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Endocrine resistance remains a significant problem in the clinical treatment of estrogen receptor α-positive (ERα + ) breast cancer (BC). In this study, we developed a series of novel dual-functional ERα degraders based on a bridged bicyclic scaffold with selenocyano (SeCN) side chains. These compounds displayed potent ERα degradation and tubulin depolymerization activity. Among them, compounds 35s and 35t exhibited the most promising antiproliferative and ERα degradation activity in multiple ERα + BC cell lines bearing either wild-type or mutant ERα. Meanwhile, compounds 35s and 35t disrupted the microtubule network by restraining tubulin polymerization, evidenced by 35t inducing cell cycle arrest in the G2/M phase. In MCF-7 and LCC2 xenograft models, compounds 35s and 35t remarkably suppressed tumor growth without noticeable poisonousness. Finally, this study provided guidance for developing new dual-target antitumor drug candidates for the ERα + BC therapy, especially for the resistant variant.

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“…Hormone-sensitive BC, the most prevalent non-cutaneous cancer subtype in women globally, evolves due to malfunction in the steroidogenic machinery, in which estrogen and its receptors play vital roles in their progression and survival [10][11][12][13]. In accordance with this, the majority of BCs (~80%) express either estrogen receptor (ER+), especially ERα (ESR1), progesterone receptor (PR+), and human epidermal growth factor receptor 2/the erythroblastosis oncogene-B2 (HER2/ErbB2+), or all three, in which E2 is critical for maintenance of these luminal subtype BCs [7,9].…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of StAR in Cancerous and Non-Cancerous Human and Mouse Breast Tissues: New Insights into Diagnosis and Treatment of Hormone-Sensitive Breast Cancer

Manna

Ramachandran

Pradeepkiran

et al. 2023

IJMS

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Breast cancer (BC) is primarily triggered by estrogens, especially 17β-estradiol (E2), which are synthesized by the aromatase enzyme. While all steroid hormones are derived from cholesterol, the rate-limiting step in steroid biosynthesis is mediated by the steroidogenic acute regulatory (StAR) protein. Herein, we demonstrate that StAR mRNA expression was aberrantly high in human hormone-dependent BC (MCF7, MDA-MB-361, and T-47D), modest in hormone-independent triple negative BC (TNBC; MDA-MB-468, BT-549, and MDA-MB-231), and had little to none in non-cancerous mammary epithelial (HMEC, MCF10A, and MCF12F) cells. In contrast, these cell lines showed abundant expression of aromatase (CYP19A1) mRNA. Immunofluorescence displayed qualitatively similar patterns of both StAR and aromatase expression in various breast cells. Additionally, three different transgenic (Tg) mouse models of spontaneous breast tumors, i.e., MMTV-Neu, MMTV-HRAS, and MMTV-PyMT, demonstrated markedly higher expression of StAR mRNA/protein in breast tumors than in normal mammary tissue. While breast tumors in these mouse models exhibited higher expression of ERα, ERβ, and PR mRNAs, their levels were undetected in TNBC tumors. Accumulation of E2 in plasma and breast tissues, from MMTV-PyMT and non-cancerous Tg mice, correlated with StAR, but not with aromatase, signifying the importance of StAR in governing E2 biosynthesis in mammary tissue. Treatment with a variety of histone deacetylase inhibitors (HDACIs) in primary cultures of enriched breast tumor epithelial cells, from MMTV-PyMT mice, resulted in suppression of StAR and E2 levels. Importantly, inhibition of StAR, concomitant with E2 synthesis, by various HDACIs, at clinical and preclinical doses, in MCF7 cells, indicated therapeutic relevance of StAR in hormone-dependent BCs. These findings provide insights into the molecular events underlying the differential expression of StAR in human and mouse cancerous and non-cancerous breast cells/tissues, highlighting StAR could serve not only as a novel diagnostic maker but also as a therapeutic target for the most prevalent hormone-sensitive BCs.

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An overview on Estrogen receptors signaling and its ligands in breast cancer

Cited by 48 publications

References 187 publications

Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex

Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex

Identification of Novel Dual-Target Estrogen Receptor α Degraders with Tubulin Inhibitory Activity for the Treatment of Endocrine-Resistant Breast Cancer

Expression and Function of StAR in Cancerous and Non-Cancerous Human and Mouse Breast Tissues: New Insights into Diagnosis and Treatment of Hormone-Sensitive Breast Cancer

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