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Estrogen receptor alpha

A Aydogan, O Ozmen, M Haligur, C Sipahi, D Ileri, A Haligur
We investigated the expression of bcl-2, estrogen receptor alpha (ER-alpha), caspase-3, -8, -9, proliferating cell nuclear antigen (PCNA) and Ki-67 in canine mammary carcinomas. We used 65 paraffin embedded and re-diagnosed archival canine mammary tumor samples to which we applied the routine streptavidin-biotin-peroxidase technique. Seventeen cases were re-diagnosed as tubulopapillary carcinoma, 31 were re-diagnosed as complex carcinoma and 17 were re-diagnosed as carcinosarcoma. Differences of expression of bcl-2 and PCNA were statistically significant according to tumor type...
March 22, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Hung-Wen Tsai, Chung-Liang Ho, Shu-Wen Cheng, Yih-Jyh Lin, Chou-Cheng Chen, Pin-Nan Cheng, Chia-Jui Yen, Ting-Tsung Chang, Po-Min Chiang, Shih-Huang Chan, Cheng-Hsun Ho, Shu-Hui Chen, Yi-Wen Wang, Nan-Haw Chow, Jou-Chun Lin
AIM: To investigate the clinicopathological significance of progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 in hepatocellular carcinoma (HCC). METHODS: We performed immunohistochemical staining to evaluate the estrogen receptor (ER), progesterone receptor (PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data ( n = 373) from The Cancer Genome Atlas (TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients...
March 14, 2018: World Journal of Gastroenterology: WJG
George S Tria, Tinya Abrams, Jason Baird, Heather E Burks, Brant Firestone, L Alex Gaither, Lawrence G Hamann, Guo He, Christina A Kirby, Sunkyu Kim, Franco Lombardo, Kaitlin J Macchi, Donald P McDonnell, Yuji Mishina, John D Norris, Jill Nunez, Clayton Springer, Yingchuan Sun, Noel M Thomsen, Chunrong Wang, Jianling Wang, Bing Yu, Choi-Lai Tiong-Yip, Stefan Peukert
In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies...
March 22, 2018: Journal of Medicinal Chemistry
Michael F Sweeney, Carlos Sonnenschein, Ana M Soto
Background: Three-dimensional cultures of mammary epithelial cells allow for biologically-relevant studies of the development of the mammary gland in rodents and humans under normal and pathological conditions, like carcinogenesis. Under these conditions, mammotropic hormones play significant roles in tissue morphogenesis. Therefore, a system that recreates the normal, hormonally responsive epithelium would be a valuable tool to study the normal state and its transition to carcinogenesis...
2018: Cancer Cell International
Geetha Rani Yuvaraj, Baddrireddi Subhadra Lakshmi
Estrogen receptor α (ER α) is an important therapeutic target in the regulation of ligand dependent signaling in breast cancer. The current study investigates the anti-estrogenic potential of the Diarylheptanoid, 5-hydroxy-7-(4-hydroxy-3 methoxyphenyl)-1-phenyl-3-heptanone (DAH) in silico. Rigid Docking analysis of DAH at the ligand binding domain (LBD) of ER α showed hydrogen bond interactions with Arg394 and Glu353 at the active site, similar to the positive controls 4 - Hydroxy Tamoxifen (4-OHT) and Fulvestrant (FUL)...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Hayato Kaida, Koichi Azuma, Uhi Toh, Akihiko Kawahara, Eiji Sadashima, Satoshi Hattori, Jun Akiba, Nobuhiro Tahara, Axel Rominger, Kazunai Ishii, Takamichi Murakami, Masatoshi Ishibashi
OBJECTIVE: To assess the correlations between dual-phase fluorine-18 fluorodeoxyglucose (18 F-FDG) uptake and clinicopathological and immunohistochemical prognostic factors in patients with surgically resected breast cancer. SUBJECTS AND METHODS: We retrospectively analyzed the cases of 105 patients. We calculated the maximum standardized uptake value (SUVmax) at 85min (SUV1), SUVmax at 125min (SUV2) and the retention index [RI]. Spearman's rank correlation test, the Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were performed to assess the association between18 F-FDG uptake and the clinicopathological and immunohistochemical factors: glucose transporter-1 (Glut-1), estrogen receptor alpha (ERα), ERβ, progesterone receptor (PR), human epidermal growth factor 2 (Her2), mammalian target of rapamycin (mTOR), and P70S6kinase (P70S6)...
March 20, 2018: Hellenic Journal of Nuclear Medicine
J Richard Pilsner, Alex Shershebnev, Yulia Medvedeva, Alexander Suvorov, Haotian Wu, Andrey Goltsov, Evgeny Loukianov, Tatiana Andreeva, Fedor Gusev, Andrey Manakhov, Luidmila Smigulina, Maria Logacheva, Victoria Shtratnikova, Irina Kuznetsova, Peter Speranskiy-Podobed, Jane S Burns, Paige L Williams, Susan Korrick, Mary M Lee, Evgeny Rogaev, Russ Hauser, Oleg Sergeyev
BACKGROUND: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown. OBJECTIVE: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood. METHODS: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age...
March 14, 2018: Reproductive Toxicology
Magdalena B Król, Michał Galicki, Peter Grešner, Edyta Wieczorek, Ewa Jabłońska, Edyta Reszka, Zbigniew Morawiec, Wojciech Wąsowicz, Jolanta Gromadzińska
BACKGROUND: The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. METHODS: We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients...
March 15, 2018: Acta Biochimica Polonica
Kelly Kyker-Snowman, Bracha Erlanger Avigdor, Mansoor Nasim, Ashley Cimino-Mathews, Sarah J Wheelan, Pedram Argani, Ben Ho Park
BACKGROUND/PURPOSE: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative...
March 15, 2018: Breast Cancer Research and Treatment
Laura Lupini, Anna Moretti, Cristian Bassi, Alessio Schirone, Massimo Pedriali, Patrizia Querzoli, Roberta Roncarati, Antonio Frassoldati, Massimo Negrini
Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0...
March 12, 2018: Scientific Reports
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβO), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. AβO infusion evoked a sustained inflammatory response including activation of NF-κB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors...
March 6, 2018: Neuroscience
Carmela Ricciardelli, Tina Bianco-Miotto, Shalini Jindal, Lisa M Butler, Samuel Leung, Catriona M McNeil, Sandra A O'Toole, Esmaeil Ebrahimie, Ewan K A Millar, Andrew J Sakko, Alexandra I Ruiz, Sarah L Vowler, David G Hunstman, Stephen N Birrell, Robert L Sutherland, Carlo Palmieri, Theresa Hickey, Wayne D Tilley
PURPOSE: Consensus is lacking regarding the androgen receptor (AR) as a prognostic marker in breast cancer. The objectives of this study were to comprehensively review the literature on AR prognostication and determine optimal criteria for AR as an independent predictor of breast cancer survival. EXPERIMENTAL DESIGN: AR positivity was assessed by immunostaining in two clinically-validated primary breast cancer cohorts (training cohort n=219; validation cohort n=418; 77% and 79% estrogen receptor alpha (ERα) positive, respectively)...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Eugenia Morselli, Roberta de Souza Santos, Su Gao, Yenniffer Ávalos, Alfredo Criollo, Biff F Palmer, Deborah J Clegg
Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Wei Yang, Gary N Schwartz, Jonathan D Marotti, Vivian Chen, Nicole A Traphagen, Jiang Gui, Todd W Miller
The mTORC1 inhibitor RAD001 (everolimus) is approved for treatment of recurrent/metastatic estrogen receptor (ER)-positive breast cancer in combination with the aromatase inhibitor (AI) exemestane. The benefits of A) continued anti-estrogen therapy for anti-estrogen-resistant disease in the context of mTORC1 inhibition, and B) adjuvant everolimus in combination with anti-estrogen therapy for early-stage disease are being tested clinically, but molecular rationale remains unclear. We hypothesized that mTORC1 inhibition activates the IGF-1R/InsR/IRS-1/2 axis in an ER-dependent manner to drive PI3K/AKT and promote cancer cell survival, implicating ER in survival signaling induced by mTORC1 inhibition...
February 6, 2018: Oncotarget
Ana Cicvaric, Jiaye Yang, Tanja Bulat, Alice Zambon, Manuel Dominguez-Rodriguez, Rebekka Kühn, Michael G Sadowicz, Anjana Siwert, Joaquim Egea, Daniela D Pollak, Thomas Moeslinger, Francisco J Monje
The Fibronectin Leucine-Rich Transmembrane protein 2 (FLRT2) has been implicated in several hormone -and sex-dependent physiological and pathological processes (including chondrogenesis, menarche and breast cancer); is known to regulate developmental synapses formation, and is expressed in the hippocampus, a brain structure central for learning and memory. However, the role of FLRT2 in the adult hippocampus and its relevance in sex-dependent brain functions remains unknown. We here used adult single-allele FLRT2 knockout (FLRT2+/- ) mice and behavioral, electrophysiological, and molecular/biological assays to examine the effects of FLRT2 haplodeficiency on synaptic plasticity and hippocampus-dependent learning and memory...
February 27, 2018: Scientific Reports
Anna Kjerstine Rosenmai, Frida Niss, Geeta Mandava, Johan Lundqvist, Agneta Oskarsson
Surface water can be contaminated with pollutants from multiple sources and contain a vast number of various chemicals. In vitro bioassays are valuable tools to assess the total bioactivity of micropollutants in water samples. Besides anthropogenic chemicals, natural organic matter (NOM) is ubiquitous in water, which also may have an impact on the bioactivity in water samples. In the present study we investigated concentration-dependent effects of Nordic Aquatic fulvic acid (NA-FA) and Nordic reservoir NOM (NR-NOM) on bioactivity measured by a panel of luciferase reporter gene assays...
February 14, 2018: Chemosphere
A O Adebayo, A K Akinloye, A O Ihunwo, V O Taiwo, B O Oke
The excurrent duct, which plays vital roles in the reproductive biology of all male mammals, shows some structural variations among different species. Some hormones such as testosterone, estrogen and progesterone, through their different receptors, have been known to be involved in the normal functioning of the excurrent duct. Here we evaluated the presence, localization and patterns of distribution of three hormone receptors, estrogen alpha (ERα), estrogen beta (ERβ) receptors and progesterone receptors (PR) along the excurrent duct of sexually matured male greater cane rats...
December 30, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
Haifei Chen, Jiewen Pan, Liudi Zhang, Lu Chen, Huijie Qi, Mingkang Zhong, Xiaojin Shi, Juan Du, Qunyi Li
Estrogen-related receptor alpha (ERRα), one of orphan nuclear receptors, has been recently revealed as an oncogenic regulator in a variety of cancers. However, the linking gain of ERRα expression and cancer progression in cutaneous squamous cell carcinoma (cSCC) is largely unknown. Here, we showed that the mRNA and protein expression levels of ERRα were markedly higher in A431 cells compared with human keratinocyte cell line HaCaT, and targeted inhibition of ERRα by shRNA or its inverse agonist XCT790 significantly suppressed A431 cells proliferation and migration, while overexpression of ERRα promoted cell proliferation and migration...
February 21, 2018: European Journal of Pharmacology
Dimitrios Zardavas, Luc Te Marvelde, Roger L Milne, Debora Fumagalli, George Fountzilas, Vassiliki Kotoula, Evangelia Razis, George Papaxoinis, Heikki Joensuu, Mary Ellen Moynahan, Bryan T Hennessy, Ivan Bieche, Lao H Saal, Olle Stal, Barry Iacopetta, Jeanette Dupont Jensen, Sandra O'Toole, Elena Lopez-Knowles, Mattia Barbaraeschi, Shinzaburo Noguchi, Hatem A Azim, Enrique Lerma, Thomas Bachelot, Qing Wang, Gizeh Perez-Tenorio, Cornelis J H Can de Velde, Daniel W Rea, Vicky Sabine, John M S Bartlett, Christos Sotiriou, Stefan Michiels, Sherene Loi
Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study...
February 22, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Julie Johnson, Darrell C Bessette, Jodi M Saunus, Chanel E Smart, Sarah Song, Rebecca L Johnston, Sibylle Cocciardi, Esdy N Rozali, Cameron N Johnstone, Ana Christina Vargas, Stephen H Kazakoff, Victorian Cancer BioBank, Kum Kum Khanna, Sunil R Lakhani, Georgia Chenevix-Trench, Peter T Simpson, Katia Nones, Nicola Waddell, Fares Al-Ejeh
PURPOSE: We aimed to generate and characterize a novel cell line from a breast cancer bone metastasis to better study the progression of the disease. METHODS: The cell line, P7731, was derived from a metastatic bone lesion of a breast cancer patient and assessed for marker expression. P7731 was analyzed for DNA copy number variation, somatic mutations, and gene expression and was compared with the primary tumor. RESULTS: P7731 cells are negative for estrogen receptor alpha (ERα), progesterone receptor (PR), and HER2 (triple-negative); strongly express vimentin (100% of cells positive) and also express cytokeratins 8/18 and 19 but at lower frequencies...
February 21, 2018: Breast Cancer Research and Treatment
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