Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

Ikeda, Kazuhiro; Horie‐Inoue, Kuniko; Inoue, Satoshi

doi:10.1038/aps.2014.123

Cited by 82 publications

(52 citation statements)

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“…Microarray and high throughput sequencing were widely used to detect and quantify the transcriptomic profile of the human genome, which is useful in the identification of target genes of interest for diagnosing or treating NFPAs (26).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients

Cheng

Wang

et al. 2019

Front. Endocrinol.

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Background: Non-functional pituitary adenoma (NFPA) is a common tumor that occurs in the pituitary gland, and generally without any symptoms at its early stage and without clinical elevation of hormones, which is commonly diagnosed when it grows up to compress its surrounding tissues and organs. Currently, the pathogenesis of NFPA has not been clarified yet. It is necessary to investigate molecular alterations in NFPA, and identify reliable biomarkers and drug therapeutic targets for effective treatments.Methods: Tandem mass tags (TMT)-based quantitative proteomics was used to identify and quantify proteins in NFPAs. GO and KEGG enrichment analyses were used to analyze the identified proteins. Differentially expressed genes (DEGs) between NFPA and control tissues were obtained from GEO datasets. These two sets of protein and gene data were analyzed to obtain overlapped molecules (genes; proteins), followed by further GO and KEGG pathway analyses of these overlapped molecules, and molecular network analysis to obtain the hub molecules with Cytoscape. Two hub molecules (SRC and AKT1) were verified with Western blotting.Results: Totally 6076 proteins in NFPA tissues were identified, and 3598 DEGs between NFPA and control tissues were identified from GEO database. Overlapping analysis of 6076 proteins and 3598 DEGs obtained 1088 overlapped molecules (DEGs; proteins). KEGG pathway analysis of 6076 proteins obtained 114 statistically significant pathways, including endocytosis, and spliceosome signaling pathways. KEGG pathway analysis of 1088 overlapped molecules obtained 52 statistically significant pathways, including focal adhesion, cGMP-PKG pathway, and platelet activation signaling pathways. These pathways play important roles in cell energy supply, adhesion, and maintenance of the tumor microenvironment. According to the association degree in Cytoscape, ten hub molecules (DEGs; proteins) were identified, including GAPDH, ALB, ACACA, SRC, ENO2, CALM1, POTEE, HSPA8, DECR1, and AKT1. Western-blotting analysis confirmed the upregulated expressions of SRC and PTMScan experiment confirmed the increased levels of pAKT1, in NFPAs compared to controls.Cheng et al. Non-functional Pituitary Adenoma Proteomic ProfilingConclusions: This study established the large-scale quantitative protein profiling of NFPA tissue proteome. It offers a basis for subsequent in-depth proteomics analysis of NFPAs, and insight into the molecular mechanism of NFPAs. It also provided the basic data to discover reliable biomarkers and therapeutic targets for NFPA patients.

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Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients

Cheng

Wang

et al. 2019

Front. Endocrinol.

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“…The emergence of sex-specific traits likely involves modifications in sexually dimorphic gene expression patterns, which may be driven by sex-dependent gene regulation (Blekhman et al, 2010; Ober et al, 2008; Williams and Carroll, 2009). Ligand-dependent transcriptional regulation by steroid sex hormones and their receptors was suggested to play a role in sexual development and reproductive function by mediating downstream target gene expression with other TFs (Bouman et al, 2005; Ikeda et al, 2015; Verthelyi, 2001). To our surprise, we did not observe significant differences in gene expression of steroid hormone receptors between men and women in most of the analyzed tissues.…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphism in gene expression and regulatory networks across human tissues

Chen

Lopes‐Ramos

Kuijjer

et al. 2016

Preprint

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SummarySexual dimorphism manifests in many diseases and may drive sex-specific therapeutic responses. To understand the molecular basis of sexual dimorphism, we conducted a comprehensive assessment of gene expression and regulatory network modeling in 31 tissues using 8716 human transcriptomes from GTEx. We observed sexually dimorphic patterns of gene expression involving as many as 60% of autosomal genes, depending on the tissue. Interestingly, sex hormone receptors do not exhibit sexually dimorphic expression in most tissues; however, differential network targeting by hormone receptors and other transcription factors (TFs) captures their downstream sexually dimorphic gene expression. Furthermore, differential network wiring was found extensively in several tissues, particularly in brain, in which not all regions exhibit strong differential expression. This systems-based analysis provides a new perspective on the drivers of sexual dimorphism, one in which a repertoire of TFs plays important roles in sex-specific rewiring of gene regulatory networks.HighlightsSexual dimorphism manifests in both gene expression and gene regulatory networksSubstantial sexual dimorphism in regulatory networks was found in several tissuesMany differentially regulated genes are not differentially expressedSex hormone receptors do not exhibit sexually dimorphic expression in most tissues

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“…The first article by Tan and coworkers will provide comprehensive review on structures, diseases relevance and drug discovery of androgen receptor, the oncogenic driver of prostate cancer [1] . The second review article by Ikeda and coworkers covers the roles of estrogen-responsive genes in breast cancer [2] . Beside androgen receptor and estrogen receptor, the two of classical steroid hormone receptors in cancers, orphan nuclear receptors COUPTFs also known to play important role in tumorigenesis, and they are respectively reviewed by Xu and coworkers [3] .…”

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confidence: 99%

Family reunion of nuclear hormone receptors: structures, diseases, and drug discovery

2015

Acta Pharmacol Sin

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EditorialHormones comprise one of the most effective classes of messengers that transmit cell to cell communication in eukaryotic systems. Cells receive messages of hormones through protein receptors, and then translate the hormone signals into concrete action of physiological responses. Homeostasis of hormone systems is essential for human health, and aberrant regulation of hormone signaling has been associated with many diseases, including cancer, diabetes, and inflammation diseases. As such, targeting hormone signaling pathways has become a major venue of pharmacological intervention of many health abnormalities. There are two major classes of hormone receptors: G-protein coupled receptors and nuclear hormone receptors, both of which consist of the top two classes of the most successful drug targets. Two years ago, we published a special issue on structures, biology and drug discovery of G-protein coupled receptors, which has been well received by drug discovery research communities. This year marked the 30th anniversary of the cloning of the first member of the nuclear receptor family and 25th year of the discovery of orphan nuclear receptors, for which no cognate ligands were known at the time of their cloning. Since then we have witnessed a tremendous expansion of our knowledge of this family of receptors. In this special issue, we collected eleven exciting review articles, highlighting our current understanding of structure, function, disease relevance, and drug discovery of nuclear receptors.Hormones androgen and estrogen have long been known to play key roles in development, growth, and homeostasis of reproductive systems and their dysregulation is the major cause of prostate cancer and breast cancer. The first article by Tan and coworkers will provide comprehensive review on structures, diseases relevance and drug discovery of androgen receptor, the oncogenic driver of prostate cancer [1] . The second review article by Ikeda and coworkers covers the roles of estrogen-responsive genes in breast cancer [2] . Beside androgen receptor and estrogen receptor, the two of classical steroid hormone receptors in cancers, orphan nuclear receptors COUPTFs also known to play important role in tumorigenesis, and they are respectively reviewed by Xu and coworkers [3] . In addition, the roles of bile acid receptor FXR in liver cancer will be reviewed by Huang and coworkers [4] . Nuclear hormone receptors are also well known for their central roles in metabolic regulation. Classic examples are peroxisome proliferator activated receptors (PPARs) and receptors for glucocorticoids and thyroid hormone, for which roles have been well reviewed in the literatures. In this special issue, we will focus on the emerging roles of orphan nuclear receptors in metabolism. Jiao and coworkers review the regulatory role of FXR in homeostasis of hepatic triglyceride [5] . Audet-wash and Giguère review the roles of estrogen-related receptor α and γ in metabolic control and related diseases [6] . Yan and Xie review the role of constitutive...

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Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

Cited by 82 publications

References 89 publications

Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients

Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients

Sexual dimorphism in gene expression and regulatory networks across human tissues

Family reunion of nuclear hormone receptors: structures, diseases, and drug discovery

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