Dataset Information

Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research.

ABSTRACT: Estrogen receptor β (ERβ) was discovered more than 20 years ago. However, the extent and role of ERβ expression in breast cancer remain controversial, especially in the context of triple-negative breast cancer (TNBC). ERβ exists as multiple isoforms, and a series of studies has revealed an inconsistent role of ERβ isoforms in TNBC. Our recent results demonstrated contrasting functions of ERβ1 and ERβ2/β5 in TNBC. Additional research should be conducted to explore the functions of individual ERβ isoforms and develop targeted drugs according to the relevant mechanisms. Consequently, a systematic review of ERβ isoforms is necessary. In this review, we overview the structure of ERβ isoforms and detail what is known about the function of ERβ isoforms in normal mammary tissue and breast cancer. Moreover, this review highlights the divergent features of ERβ isoforms in TNBC. This review also provides insights into the implications of targeting ERβ isoforms for clinical treatment. In conclusion, this review provides a framework delineating the roles and mechanisms of different ERβ isoforms in TNBC and sheds light on future directions for basic and clinical research.

SUBMITTER: Yan S

PROVIDER: S-EPMC10626554 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research.

Yan Shunchao S Wang Jinpeng J Chen Hong H Zhang Duo D Imam Murshid M

Frontiers in cell and developmental biology 20231023

Estrogen receptor β (ERβ) was discovered more than 20 years ago. However, the extent and role of ERβ expression in breast cancer remain controversial, especially in the context of triple-negative breast cancer (TNBC). ERβ exists as multiple isoforms, and a series of studies has revealed an inconsistent role of ERβ isoforms in TNBC. Our recent results demonstrated contrasting functions of ERβ1 and ERβ2/β5 in TNBC. Additional research should be conducted to explore the functions of individual ERβ ...[more]

PMID: 37936981

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Project description:PurposeBreast cancer is a heterogeneous disease usually including four molecular subtypes such as luminal A, luminal B, HER2-enriched, and triple-negative breast cancer (TNBC). TNBC is more aggressive than other breast cancer subtypes. Despite major advances in ER-positive or HER2-amplified breast cancer, there is no targeted agent currently available for TNBC, so it is urgent to identify new potential therapeutic targets for TNBC.MethodsWe first used microarray analysis to compare gene expression profiling between TNBC and non-TNBC. Furthermore an integrated analysis was conducted based on our own and published data, leading to more robust, reproducible and accurate predictions. Additionally, we performed qRT-PCR in breast cancer cell lines to verify the findings in integrated analysis.ResultsAfter searching Gene Expression Omnibus database (GEO), two microarray studies were obtained according to the inclusion criteria. The integrated analysis was conducted, including 30 samples of TNBC and 77 samples of non-TNBC. 556 genes were found to be consistently differentially expressed (344 up-regulated genes and 212 down-regulated genes in TNBC). Functional annotation for these differentially expressed genes (DEGs) showed that the most significantly enriched Gene Ontology (GO) term for molecular functions was protein binding (GO: 0005515, P = 6.09E-21), while that for biological processes was signal transduction (GO: 0007165, P = 9.46E-08), and that for cellular component was cytoplasm (GO: 0005737, P = 2.09E-21). The most significant pathway was Pathways in cancer (P = 6.54E-05) based on Kyoto Encyclopedia of Genes and Genomes (KEGG). DUSP1 (Degree = 21), MYEOV2 (Degree = 15) and UQCRQ (Degree = 14) were identified as the significant hub proteins in the protein-protein interaction (PPI) network. Five genes were selected to perform qRT-PCR in seven breast cancer cell lines, and qRT-PCR results showed that the expression pattern of selected genes in TNBC lines and non-TNBC lines was nearly consistent with that in the integrated analysis.ConclusionThis study may help to understand the pathogenesis of different breast cancer subtypes, contributing to the successful identification of therapeutic targets for TNBC.

Project description:Breast cancer is the most commonly diagnosed cancer (estimated 2.3 million new cases in 2020) and the leading cause of cancer death (estimated 685,000 deaths in 2020) in women globally. Breast cancers have been categorized into four major molecular subtypes based on the immunohistochemistry (IHC) expression of classic hormone and growth factor receptors including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as a proliferation marker Ki-67 protein expression. Triple-negative breast cancer (TNBC), a breast cancer subtype lacking ER, PR, and HER2 expression, is associated with a high metastatic potential and poor prognosis. TNBC accounts for approximately only 15%-20% of new breast cancer diagnoses; it is responsible for most breast cancer-related deaths due to the lack of targeted treatment options for this patient population, and currently, systemic chemotherapy, radiation, and surgical excision remain the major treatment modalities for these patients with TNBC. Although breast cancer patients in general do not have a robust response to the immunotherapy, a subset of TNBC has been demonstrated to have high tumor mutation burden and high tumor-infiltrating lymphocytes, resembling the features observed on melanoma or lung cancers, which can benefit from the treatment of immune checkpoint inhibitors (ICIs). Therefore, the immunogenic nature of this aggressive disease has presented an opportunity for the development of TNBC-targeting immunotherapies. The recent US Food and Drug Administration approval of atezolizumab in combination with the chemotherapeutic agent nab-paclitaxel for the treatment of PD-L1-positive unresectable, locally advanced, or metastatic TNBC has led to a new era of immunotherapy in TNBC treatment. In addition, immunotherapy becomes an active research area, both in the cancer biology field and in the oncology field. In this review, we will extend our coverage on recent discoveries in preclinical research and early results in clinical trials from immune molecule-based therapy including cytokines, monoclonal antibodies, antibody-drug conjugates, bi-specific or tri-specific antibodies, ICIs, and neoantigen cancer vaccines; oncolytic virus-based therapies and adoptive immune cell transfer-based therapies including TIL, chimeric antigen receptor-T (CAR-T), CAR-NK, CAR-M, and T-cell receptor-T. In the end, we will list a series of the challenges and opportunities in immunotherapy prospectively and reveal novel technologies such as high-throughput single-cell sequencing and CRISPR gene editing-based screening to generate new knowledges of immunotherapy.

Dataset Information

Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research.

Publications

Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research.

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