Estrogen Receptor Beta 1: A Potential Therapeutic Target for Triple Negative Breast Cancer
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ABSTRACT:
PROVIDER: PRJNA863644 | ENA |
REPOSITORIES: ENA
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Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). These receptors are well characterized and often serve as targets in breast cancer treatment. As a result, TNBCs are difficult to treat and have a high propensity to metastasize to distant organs. For these reasons, TNBCs are responsible for over 50% of all breast cancer mortalities while only accounting for 15% - 20% of breast cancer cases. However, estrogen receptor beta 1 (ERβ1) has emerged as a potential therapeutic target in the treatment of TNBCs. Using an in vivo xenograft preclinical mouse model with human TNBC, we found that expression of ERβ1 significantly reduced both primary tumor growth and metastasis in the animals. Moreover, TNBCs with elevated levels of ERβ1 showed reduction in epithelial-to-mesenchymal transition (EMT) markers and breast cancer stem cell (BCSC) markers, and increases in the expression of genes associated with inhibition of cancer cell invasiveness and metastasis, suggesting possible mechanisms underlying the antitumor activity of ERβ1. Treatment with ERβ1 agonist ligand often enhanced the suppressive activity of ERβ1, suggesting their potential utility in improving TNBC treatment. The findings enable understanding of the mechanisms by which ERβ impedes TNBC growth, invasiveness and metastasis and consideration of ways by which treatments involving ERβ might improve TNBC patient outcome.
2022-10-28 | GSE210092 | GEO
Project description:The goal of this work was to identify all estrogen receptor beta target genes using RNA sequencing in MDA-MB-468 triple negative breast cancer cells engineered with inducible expression of full length estrogen receptor beta.
2015-08-12 | GSE71960 | GEO
Project description:The goal of this work was to identify all estrogen receptor beta target genes using RNA sequencing in MDA-MB-468 triple negative breast cancer cells engineered with inducible expression of full length estrogen receptor beta. MDA-MB-468 breast cancer cells with inducible ERb expression (MDA-468-ERb cells) were treated in triplicate with vehicle (control, no ERb) or doxycycline (plus ERb) for 48 hr prior to treatment with 0.1% DMSO vehicle or 10 nM 17b-estradiol for 4 hr.
2015-08-12 | E-GEOD-71960 | biostudies-arrayexpress
Project description:Breast cancer (BC) is the second most common type of cancer in women and one of the leading causes of cancer-related deaths worldwide. BC classification is based on the detection of three main histological markers: estrogen receptor alpha (ERα), progesterone receptor (PR) and the amplification of epidermal growth factor receptor 2 (HER2/neu). A specific BC subtype, named triple-negative BC (TNBC), lacks the aforementioned markers but a fraction of them express the estrogen receptor beta (ERβ). To investigate the functional role of ERβ in these tumors, interaction proteomics coupled to mass spectrometry (MS) was applied to deeply characterize the nuclear interactors partners in MDA-MD-468 and HCC1806 TNBC cells.
2019-12-03 | PXD014468 | Pride
Project description:Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer
| PRJNA638951 | ENA
Project description:Breast cancer (BC) is the most common cancer in women worldwide, and is classified in multiple subtypes, including the so called triple-negative BC (TNBC). This is characterized by lack of estrogen receptor alpha (ERα), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), that represent common targets for BC treatment. Their absence limits the number of therapies that may be applied for TNBC treatment, suggesting the need to identify novel therapeutic targets against this disease. Several studies reported that the beta ER subtype (ERβ) is expressed in a sizeable fraction of TNBCs where its presence correlates with improved patient outcome. We evaluated ERβ expression in TNBC tissues by immunohistochemistry using two validated antibodies, demonstrating presence of this protein in 28% of samples. To investigate, in this context, the role of this estrogen receptor in TNBC biology, ERβ-expressing cell lines, representing different TNBC subtypes, were generated. Cellular and functional assays confirmed the antiproliferative activity of ERβ in TNBCs. Interaction proteomics revealed in BC nuclei the presence of several protein complexes associated with this receptor involved in chromatin remodeling, miRNA maturation and mRNA transcription. Transcriptome analyses pointed out tumor subtype-specific signaling pathways deregulation. Interestingly, among these the cholesterol biosynthesis pathway was commonly downregulated in all cell lines tested. Global analyses of ERβ binding to the genome showed its recruitment to regulatory sites of Sterol Regulatory Element-Binding Protein 1 (SREBP1), indicating a direct regulation of this pathway by the receptor. These findings suggest that drugs targeting components of cholesterol biosynthesis pathway may be new potential therapeutic options for TNBC treatment.
2019-12-03 | E-MTAB-8055 | biostudies-arrayexpress
Project description:Purpose: To characterize the expression of phosphatases in estrogen receptor negative breast cancer Little is known about the role of phosphatases in the major estrogen receptor negative breast cancer phenotypes (i.e. those overexpressing ERBB2 and the triple negative). We carried out microarray phosphatome profiling in 41 estrogen receptor negative (ER-) breast cancer patients (as determined by immunohistochemistry (IHC)) containing both ERBB2+ and ERBB2- in order to characterize the differences between these groups by Statistical Analysis of Microarrays (SAM). Our findings point to the importance of the MAPK and PI3K pathways in ER- BCs as some of the most differentially expressed phosphatases (like DUSP4 and DUSP6) share ERK as substrate, or regulate the PI3K pathway (INPP4B, PTEN). These observations are also confirmed by pathway and GSEA analysis. It is shown that both ER- ERBB2+ and triple negative breast cancers have a distinctive pattern of phosphatase RNA expression. Surgical specimens from primary breast cancers that were estrogen receptor negative according to immunohistochemistry
2014-06-30 | E-GEOD-51999 | biostudies-arrayexpress
Project description:We performed whole transcriptome sequencing of human monocytes that were co-cultured with estrogen receptor positive (ER+) or triple-negative (TNBC) breast cancer cell lines and studied the biological responses related to the differential gene activation in both cell types to understand how different cancer cells educate host cells to support tumor growth
2015-11-19 | GSE75130 | GEO
Project description:Breast cancer (BC) is the most common cancer in women worldwide, and is classified in multiple subtypes, including the so called triple-negative BC (TNBC). This is characterized by lack of estrogen receptor alpha (ERα), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), that represent common targets for BC treatment. Their absence limits the number of therapies that may be applied for TNBC treatment, suggesting the need to identify novel therapeutic targets against this disease. Several studies reported that the beta ER subtype (ERβ) is expressed in a sizeable fraction of TNBCs where its presence correlates with improved patient outcome. We evaluated ERβ expression in TNBC tissues by immunohistochemistry using two validated antibodies, demonstrating presence of this protein in 28% of samples. To investigate, in this context, the role of this estrogen receptor in TNBC biology, ERβ-expressing cell lines, representing different TNBC subtypes, were generated. Cellular and functional assays confirmed the antiproliferative activity of ERβ in TNBCs. Interaction proteomics revealed in BC nuclei the presence of several protein complexes associated with this receptor involved in chromatin remodeling, miRNA maturation and mRNA transcription. Transcriptome analyses pointed out tumor subtype-specific signaling pathways deregulation. Interestingly, among these the cholesterol biosynthesis pathway was commonly downregulated in all cell lines tested. Global analyses of ERβ binding to the genome showed its recruitment to regulatory sites of Sterol Regulatory Element-Binding Protein 1 (SREBP1), indicating a direct regulation of this pathway by the receptor. These findings suggest that drugs targeting components of cholesterol biosynthesis pathway may be new potential therapeutic options for TNBC treatment.
2019-12-02 | E-MTAB-8056 | biostudies-arrayexpress
Project description:Purpose: To characterize the expression of phosphatases in estrogen receptor negative breast cancer Little is known about the role of phosphatases in the major estrogen receptor negative breast cancer phenotypes (i.e. those overexpressing ERBB2 and the triple negative). We carried out microarray phosphatome profiling in 41 estrogen receptor negative (ER-) breast cancer patients (as determined by immunohistochemistry (IHC)) containing both ERBB2+ and ERBB2- in order to characterize the differences between these groups by Statistical Analysis of Microarrays (SAM). Our findings point to the importance of the MAPK and PI3K pathways in ER- BCs as some of the most differentially expressed phosphatases (like DUSP4 and DUSP6) share ERK as substrate, or regulate the PI3K pathway (INPP4B, PTEN). These observations are also confirmed by pathway and GSEA analysis. It is shown that both ER- ERBB2+ and triple negative breast cancers have a distinctive pattern of phosphatase RNA expression.
2014-06-30 | GSE51999 | GEO