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Xingkai An, Jie Fang, Qing Lin, Congxia Lu, Qilin Ma, Hongli Qu
Migraine is a common and disabling nervous system disease with a significant genetic predisposition. The sex hormones play an important role in the pathogenesis of migraine. However, the conclusions of the previous genetic relation studies are conflicting. The aim of this study is to determine whether variants in genes involved in estrogen receptor and estrogen hormone metabolism are related to Chinese migraine. By employing a case-control approach, 8 SNPs in the ESR1, ESR2, and CYP19A1 genes are studied in a cohort of 494 migraine cases and 533 controls...
October 24, 2016: Journal of Neurology
Lara Ianov, Ashok Kumar, Thomas C Foster
The expression of estrogen receptor alpha (ERα) varies across brain regions and changes with age and according to the previous history of estradiol exposure. ERα is regulated by a number of mechanisms including the level of mRNA (Esr1) expression. For this study, we took advantage of regional differences in hippocampal ERα expression to investigate DNA ERα promoter methylation at CpG dinucleotide sites as a potential epigenetic mechanism for regulating gene expression. Young and aged female Fischer 344 rats were ovariectomized, and Esr1 expression and ERα promoter methylation were examined in hippocampal regions CA1 and CA3, either 3 or 14 weeks following surgery...
September 28, 2016: Neurobiology of Aging
Lei Chen, Baoman Wang, ShaoPeng Wang, Jing Yang, Jerry Hu, ZhiQun Xie, Yuwei Wang, Tao Huang, Yu-Dong Cai, ZhiQun Xie
Oncogenes are genes that have the potential to cause cancer. Oncogene research can provide insight into the occurrence and development of cancer, thereby helping to prevent cancer and to design effective treatments. This study proposes a network method called the oncogene prediction method based on shortest path algorithm (OPMSP) for the identification of novel oncogenes in a large protein network built using protein-protein interaction data. Novel putative genes were extracted from the shortest paths connecting any two known oncogenes...
October 21, 2016: Protein and Peptide Letters
Maria R Rebordão, António Galvão, Pedro Pinto-Bravo, Joana Pinheiro, Sandra Gamboa, Elisabete Silva, Luísa Mateus, Graça Ferreira-Dias
Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin F2α, E2 and I2 synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration...
September 8, 2016: Theriogenology
Piera Rizzolo, Anna Sara Navazio, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Marco Scarnò, Stefania Tommasi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from its largely known female counterpart. We aimed at investigating whether MBC cases harbor somatic alterations of genes known as prognostic biomarkers and molecular therapeutic targets in female breast cancer.We examined 103 MBC cases, all characterized for germ-line BRCA1/2 mutations, for somatic alterations in PIK3CA, EGFR, ESR1 and CCND1 genes.Pathogenic mutations of PIK3CA were detected in 2% of MBCs...
September 27, 2016: Oncotarget
Gary K Scott, David Chu, Ravneet Kaur, Julia Malato, Daniel E Rothschild, Katya Frazier, Serenella Eppenberger-Castori, Byron Hann, Ben Ho Park, Christopher C Benz
ERα phosphorylation at hinge site S294 (pS294) was recently shown to be essential for ER-dependent gene transcription and mediated by an unknown cyclin-dependent kinase (CDK). This study was undertaken to identify the exact CDK pathway mediating pS294 formation, and to determine if this phosphorylation event occurs with, and can be targeted to treat, the ligand-independent growth of breast cancers expressing endocrine-refractory ESR1 mutations. Using a newly developed anti-pS294 monoclonal antibody, a combination of CDK specific siRNA knockdown studies and a broad panel of CDK selective inhibitors against ligand (E2)-stimulated MCF7 cells, we first identified CDK2 as the primary mediator of pS294 formation and showed that CDK2-selective inhibitors like Dinaciclib, but not CDK4/6 inhibitors like Palbociclib, can selectively prevent pS294 formation and repress ER-dependent gene expression...
October 18, 2016: Oncotarget
Sanaz Tabarestani, Marzieh Motallebi, Mohammad Esmaeil Akbari
CONTEXT: Breast cancer is the most common cancer in women worldwide. Estrogen receptor (ER) positive breast cancer constitutes the majority of these cancers. Hormone therapy has significantly improved clinical outcomes for early- and late-stage hormone receptor positive breast cancer. Although most patients with early stage breast cancer are treated with curative intent, approximately 20% - 30% of patients eventually experience a recurrence. During the last two decades, there have been tremendous efforts to understand the biological mechanisms of hormone therapy resistance, with the ultimate goal of implementing new therapeutic strategies to improve the current treatments for ER positive breast cancer...
August 2016: Iranian Journal of Cancer Prevention
Sarah Hrebien, Ben O'Leary, Matthew Beaney, Gaia Schiavon, Charlotte Fribbens, Amarjit Bhambra, Richard Johnson, Isaac Garcia-Murillas, Nicholas Turner
Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection...
2016: PloS One
O A Melkozerova, N V Bashmakova, E V Volkova, T B Tretyakova, P B Tsyvian
The objective of the study is to assess NOS3 and ESR1 gene polymorphism in adolescent girls born with low birth weight (LBW) and suffered by anomalous uterine bleeding (AUB). A total 95 adolescent girls were studied including 32 born with LBW and AUB; 36 girls with normal birth weight and AUB; and 27 healthy girls. Single allele gene polymorphism NOS3 786T > C, 894G > T, ESR1 351A > G and 397T > C was studied. The existence of polymorphous allele С gene NOS3 786Т > С (for homozygote OR = 2...
October 2016: Gynecological Endocrinology
James N Ingle, Fang Xie, Matthew J Ellis, Paul E Goss, Lois E Shepherd, Judith-Anne W Chapman, Bingshu E Chen, Michiaki Kubo, Yoichi Furukawa, Yukihide Momozawa, Vered Stearns, Kathleen I Pritchard, Poulami Barman, Erin E Carlson, Matthew P Goetz, Richard M Weinshilboum, Krishna R Kalari, Liewei Wang
Genetic risks in breast cancer remain only partly understood. Here we report the results of a genome-wide association study of germline DNA from 4,658 women, including 252 women experiencing a breast cancer recurrence, who were entered on the MA.27 adjuvant trial comparing the aromatase inhibitors (AI) anastrozole and exemestane. Single nucleotide polymorphisms (SNP) of top significance were identified in the gene encoding MIR2052HG, a long noncoding RNA of unknown function. Heterozygous or homozygous individuals for variant alleles exhibited a ~40% or ~63% decrease, respectively, in the hazard of breast cancer recurrence relative to homozygous wild-type individuals...
October 10, 2016: Cancer Research
Anita Muthukaruppan, Annette Lasham, Kathryn J Woad, Michael A Black, Cherie Blenkiron, Lance D Miller, Gavin Harris, Nicole McCarthy, Michael P Findlay, Andrew N Shelling, Cristin G Print
BACKGROUND: Molecular markers have transformed our understanding of the heterogeneity of breast cancer and have allowed the identification of genomic profiles of estrogen receptor (ER)-α signaling. However, our understanding of the transcriptional profiles of ER signaling remains inadequate. Therefore, we sought to identify the genomic indicators of ER pathway activity that could supplement traditional immunohistochemical (IHC) assessments of ER status to better understand ER signaling in the breast tumors of individual patients...
September 13, 2016: Clinical Breast Cancer
Valérie Bernard, Sakina Kherra, Bruno Francou, Jérôme Fagart, Say Viengchareun, Jérôme Guéchot, Asmahane Ladjouze, Anne Guiochon-Mantel, Kenneth S Korach, Nadine Binart, Marc Lombès, Sophie Christin-Maitre
CONTEXT: Estrogens influence many physiological processes in mammals, including reproduction. Estrogen peripheral actions are mainly mediated through estrogen receptors (ER) α and β, encoded by ESR1 and ESR2 genes, respectively. OBJECTIVE: To describe a family in which three members presented with estrogen insensitivity. DESIGN AND SETTING: Clinical evaluation, genetic and mutational analysis were performed in an academic medical center...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
A Harrod, J Fulton, V T M Nguyen, M Periyasamy, L Ramos-Garcia, C-F Lai, G Metodieva, A de Giorgio, R L Williams, D B Santos, P J Gomez, M-L Lin, M V Metodiev, J Stebbing, L Castellano, L Magnani, R C Coombes, L Buluwela, S Ali
Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations...
October 17, 2016: Oncogene
Tan Tan, Kai Zhang, Wenjun Chen
No abstract text is available yet for this article.
October 11, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
F N Fjeldheim, H Frydenberg, V G Flote, A McTiernan, A-S Furberg, P T Ellison, E S Barrett, T Wilsgaard, G Jasienska, G Ursin, E A Wist, I Thune
BACKGROUND: Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown. METHODS: We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study...
October 7, 2016: BMC Cancer
Zhaomei Mu, Naoual Benali-Furet, Georges Uzan, Anaëlle Znaty, Zhong Ye, Carmela Paolillo, Chun Wang, Laura Austin, Giovanna Rossi, Paolo Fortina, Hushan Yang, Massimo Cristofanilli
The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs...
September 30, 2016: International Journal of Molecular Sciences
Kaitlin M Johnson, Sean C Lema
Several estuaries along the Pacific Ocean coast of North America were identified recently as having elevated 4-nonylphenol (4-NP) in sediments and biota, raising concerns about reproductive impacts for wildlife given 4-NP's established estrogenic activity as an endocrine-disrupting compound. Here we characterize 4-NP mediated induction and recovery of estrogen-sensitive gene transcripts in the arrow goby (Clevelandia ios), an intertidal fish abundant in estuarine mud flats on the west coast of North America...
October 3, 2016: Environmental Toxicology
Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
M N Drehmer, D Andrade, I A Pereira, A R Marrero, Y C N Muniz, I R de Souza, S E Löfgren
BACKGROUND: Estrogens have a modulatory effect on several immune responses, many of which are correlated to autoimmune diseases. Estrogens act through binding to their receptors, and an overexpression of these receptors has been identified in patients with different autoimmune diseases. Here we analyzed the association of a putative functional genetic variant in the main estrogen receptor (ERα) gene (ESR1), and the susceptibility to clinical findings and severity of SLE. METHODS: A total of 426 individuals (266 healthy controls and 160 SLE patients) were genotyped for the polymorphism rs2234693 in the ESR1 gene...
September 27, 2016: Lupus
D Fumagalli, T R Wilson, R Salgado, X Lu, J Yu, C O'Brien, K Walter, L Y Huw, C Criscitiello, I Laios, V Jose, D N Brown, F Rothé, M Maetens, D Zardavas, P Savas, D Larsimont, M J Piccart-Gebhart, S Michiels, M R Lackner, C Sotiriou, S Loi
BACKGROUND: Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy. MATERIALS AND METHODS: A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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