Clinical and Biological Significance of ESR1 Gene Alteration and Estrogen Receptors Isoforms Expression in Breast Cancer Patients

Nagel, Anna; Szade, Jolanta; Iliszko, Mariola; Elzanowska, Julia; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Stasiłojć, Grzegorz; Bigda, Jacek; Sądej, Rafał; Żaczek, Anna; Markiewicz, Aleksandra

doi:10.3390/ijms20081881

Cited by 8 publications

(9 citation statements)

References 36 publications

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“…Estrogen and its receptors are essential for sexual development and reproductive function. Previous studies have shown that ESR1 is closely related to the occurrence and development of various urogenital cancers [20][21][22][23], especially breast cancer [24,25] and endometrial cancer [26][27][28]. Recent studies have reported the important role of ESR1 in non-small-cell lung cancer (NSCLC) [29,30] and bladder cancer [31].…”

Section: Discussionmentioning

confidence: 99%

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

Chen

Yang

et al. 2021

Cancer Cell Int

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Background Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant hepatic tumor and has a high postoperative recurrence rate and a poor prognosis. The key roles of most tumor recurrence-associated molecules in iCCA remain unclear. This study aimed to explore hub genes related to the postsurgical recurrence of iCCA. Method Differentially expressed genes (DEGs) between iCCA samples and normal liver samples were screened from The Cancer Genome Atlas (TCGA) database and used to construct a weighted gene coexpression network. Module-trait correlations were calculated to identify the key module related to recurrence in iCCA patients. Genes in the key module were subjected to functional enrichment analysis, and candidate hub genes were filtered through coexpression and protein–protein interaction (PPI) network analysis. Validation studies were conducted to detect the “real” hub gene. Furthermore, the biological functions and the underlying mechanism of the real hub gene in iCCA tumorigenesis and progression were determined via in vitro experiments. Results A total of 1019 DEGs were filtered and used to construct four coexpression modules. The red module, which showed the highest correlations with the recurrence status, family history, and day to death of patients, was identified as the key module. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that genes in the red module were enriched in genes and pathways related to tumorigenesis and tumor progression. We performed validation studies and identified estrogen receptor 1 (ESR1), which significantly impacted the prognosis of iCCA patients, as the real hub gene related to the recurrence of iCCA. The in vitro experiments demonstrated that ESR1 overexpression significantly suppressed cell proliferation, migration, and invasion, whereas ESR1 knockdown elicited opposite effects. Further investigation into the mechanism demonstrated that ESR1 acts as a tumor suppressor by inhibiting the JAK/STAT3 signaling pathway. Conclusions ESR1 was identified as the real hub gene related to the recurrence of iCCA that plays a critical tumor suppressor role in iCCA progression. ESR1 significantly impacts the prognosis of iCCA patients and markedly suppresses cholangiocarcinoma cell proliferation, migration and invasion by inhibiting JAK/STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

Chen

Yang

et al. 2021

Cancer Cell Int

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“…Recently, Nagel and colleagues [80] studied the potential link between the amplification of the ESR1 gene and the expression of ERα36, since the decrease in DFS associated with the expression of ERα36 in their cohort was similar to the decrease in DFS associated with the amplification of the ESR1 gene as detected by qPCR. However, irrespective of the technique used, qPCR or FISH, no correlation could be established between the ESR1 gene copy number and the level of ERα36 expression.…”

Section: Transcription Factorsmentioning

confidence: 93%

The Role of ERα36 in Development and Tumor Malignancy

Thiébaut

Konan

Guerquin

et al. 2020

IJMS

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Estrogen nuclear receptors, represented by the canonical forms ERα66 and ERβ1, are the main mediators of the estrogen-dependent pathophysiology in mammals. However, numerous isoforms have been identified, stimulating unconventional estrogen response pathways leading to complex cellular and tissue responses. The estrogen receptor variant, ERα36, was cloned in 2005 and is mainly described in the literature to be involved in the progression of mammary tumors and in the acquired resistance to anti-estrogen drugs, such as tamoxifen. In this review, we will first specify the place that ERα36 currently occupies within the diversity of nuclear and membrane estrogen receptors. We will then report recent data on the impact of ERα36 expression and/or activity in normal breast and testicular cells, but also in different types of tumors including mammary tumors, highlighting why ERα36 can now be considered as a marker of malignancy. Finally, we will explain how studying the regulation of ERα36 expression could provide new clues to counteract resistance to cancer treatments in hormone-sensitive tumors.

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“…The ER subtypes, ERα and ERβ, are encoded by several genes, including ESR1 and ESR2 3 . The ESR1 gene, located on chromosome 6, encodes three isoforms of ERα, whereas the ESR2 gene, located on chromosome 14, encodes five isoforms of ERβ 6 . ERs have the capacity to alter signaling pathways in transcriptional regulation‐dependent and ‐independent manners 7 .…”

Section: Introductionmentioning

confidence: 99%

“…3 The ESR1 gene, located on chromosome 6, encodes three isoforms of ERα, whereas the ESR2 gene, located on chromosome 14, encodes five isoforms of ERβ. 6 ERs have the capacity to alter signaling pathways in transcriptional regulation-dependent and -independent manners. 7 The transcriptional activity of ERs is most commonly activated by their binding to estrogen.…”

mentioning

confidence: 99%

Nuclear hormone receptors in demyelinating diseases

Veloz

McKenzie

Palacios

et al. 2022

J Neuroendocrinology

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Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there are no disease modifying therapies that prevent the loss of myelin or promote remyelination. This review aims to summarize studies in the field that highlight the importance of nuclear hormone receptors in the promotion and maintenance of myelination and the relevance of nuclear hormone receptors as potential therapeutic targets for demyelinating diseases.These nuclear hormone receptors include the estrogen receptor, progesterone receptor, androgen receptor, vitamin D receptor, thyroid hormone receptor, peroxisome proliferator-activated receptor, liver X receptor, and retinoid X receptor. Pre-clinical studies in well-established animal models of demyelination have shown a prominent role of these nuclear hormone receptors in myelination through their promotion of oligodendrocyte maturation and development. The activation of the nuclear hormone receptors by their ligands also promotes the synthesis of myelin proteins and lipids in mouse models of demyelination. There are limited clinical studies that focus on how the activation of these nuclear hormone receptors could alleviate demyelination in patients with diseases such as multiple sclerosis (MS). However, the completed clinical trials have reported improved clinical outcome in MS patients treated with the ligands of some of these nuclear hormone receptors. Together, the positive results from both clinical and pre-clinical studies point to nuclear hormone receptors as promising therapeutic targets to counter demyelination.

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Clinical and Biological Significance of ESR1 Gene Alteration and Estrogen Receptors Isoforms Expression in Breast Cancer Patients

Cited by 8 publications

References 36 publications

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

The Role of ERα36 in Development and Tumor Malignancy

Nuclear hormone receptors in demyelinating diseases

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