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H Zhao, J Wang, D Fang, O Lee, R T Chatterton, V Stearns, S A Khan, S E Bulun
Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese...
March 15, 2018: Hormones & Cancer
Lan Hai, Maria M Szwarc, Bin He, David M Lonard, Ramakrishna Kommagani, Francesco J DeMayo, John P Lydon
Speckle-type poz protein (SPOP) is an E3-ubiquitin ligase adaptor for turnover of a diverse number of proteins involved in key cellular processes from chromatin remodeling, transcriptional regulation to cell signaling. Genomic analysis revealed that SPOP somatic mutations are found in a subset of endometrial cancers, suggesting that these mutations act as oncogenic drivers of this gynecologic malignancy. These studies also raise the question as to the role of wild type SPOP in normal uterine function. To address this question, we generated a mouse model (Spopd/d) in which SPOP is ablated in uterine cells that express the PGR...
March 13, 2018: Biology of Reproduction
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
Sarah A Marshall, Jonathan T McGuane, Yu May Soh, Helen M Gehring, Emma Simpson, Laura J Parry
Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1-/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1+/+) and Rln1-/- mice...
March 14, 2018: Reproduction, Fertility, and Development
Jieun Son, Yuri Park, Sang-Hyuk Chung
Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa). Estradiol (E2 ) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin 14 (K14) promoter. E2 mainly works through estrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα-coding gene) in the cervical stroma of K14E7 mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa...
March 13, 2018: Journal of Pathology
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
Hirokazu Doi, Takashi X Fujisawa, Ryoichiro Iwanaga, Junko Matsuzaki, Chisato Kawasaki, Mamoru Tochigi, Tsukasa Sasaki, Nobumasa Kato, Kazuyuki Shinohara
BACKGROUND: Previous studies on etiology of autism spectrum disorders (ASD) have shown strong contribution of hereditary factors. On the basis the heterogeneity in ASD symptoms, it is highly possible that each independent domain of ASD symptom is linked to a different set of genetic risk factors. However, few empirical investigations have been carried out to examine this hypothesis. AIMS: The aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in estrogen receptor genes, which several previous studies have identified as potential risk factors of ASD, and the severity of each independent aspect of ASD symptom within an Asian clinical sample...
March 8, 2018: Research in Developmental Disabilities
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
S Piscuoglio, C K Y Ng, B Weigelt, S Chandarlapaty, J S Reis-Filho
No abstract text is available yet for this article.
March 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
L Montrose, V Padmanabhan, J M Goodrich, S E Domino, M C Treadwell, J D Meeker, D J Watkins, D C Dolinoy
Endocrine disrupting chemicals (EDCs) pose a public health risk through disruption of normal biological processes. Identifying toxicoepigenetic mechanisms of developmental exposure-induced effects for EDCs, such as phthalates or bisphenol A (BPA), is essential. Here, we investigate whether maternal exposure to EDCs is predictive of infant DNA methylation at candidate gene regions. In the Michigan Mother-Infant Pairs (MMIP) cohort, DNA was extracted from cord blood leukocytes for methylation analysis by pyrosequencing (n = 116) and methylation changes related to first trimester levels of 9 phthalate metabolites and BPA...
March 7, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Heglayne Pereira Vital da Silva, Gustavo Henrique de Medeiros Oliveira, Marcela Abbott Galvão Ururahy, João Felipe Bezerra, Karla Simone Costa de Souza, Raul Hernandes Bortolin, André Ducati Luchessi, Vivian Nogueira Silbiger, Valéria Morgiana Gualberto Duarte Moreira Lima, Gisele Correia Pacheco Leite, Maria Edinilma Felinto Brito, Erlane Marques Ribeiro, Vera Lúcia Gil-da-Silva-Lopes, Adriana Augusto de Rezende
BACKGROUND: Although more than 14 loci may be involved in the development of nonsyndromic cleft lip and palate (NSCLP), the etiology has not been fully elucidated due to genetic and environmental risk factor interactions. Despite advances in identifying genes associated with the NSCLP development using traditional genetic mapping strategies of candidate genes, genome-wide studies, and epidemiologic and linkage analysis, microarray techniques have become important complementary tools in the search for potential causative oral clefts genes in genetic studies...
March 7, 2018: Journal of Clinical Laboratory Analysis
Debora Sugiaman-Trapman, Morana Vitezic, Eeva-Mari Jouhilahti, Anthony Mathelier, Gilbert Lauter, Sougat Misra, Carsten O Daub, Juha Kere, Peter Swoboda
BACKGROUND: Evolutionarily conserved RFX transcription factors (TFs) regulate their target genes through a DNA sequence motif called the X-box. Thereby they regulate cellular specialization and terminal differentiation. Here, we provide a comprehensive analysis of all the eight human RFX genes (RFX1-8), their spatial and temporal expression profiles, potential upstream regulators and target genes. RESULTS: We extracted all known human RFX1-8 gene expression profiles from the FANTOM5 database derived from transcription start site (TSS) activity as captured by Cap Analysis of Gene Expression (CAGE) technology...
March 6, 2018: BMC Genomics
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
Ben O'Leary, Sarah Hrebien, James P Morden, Matthew Beaney, Charlotte Fribbens, Xin Huang, Yuan Liu, Cynthia Huang Bartlett, Maria Koehler, Massimo Cristofanilli, Isaac Garcia-Murillas, Judith M Bliss, Nicholas C Turner
CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3...
March 1, 2018: Nature Communications
José M Guzmán, J Adam Luckenbach, Denis A M da Silva, Edward S Hayman, Gina M Ylitalo, Frederick W Goetz, Penny Swanson
Pituitary-hormone signaling plays critical roles in the onset and progression of gametogenesis in vertebrates. This study characterized expression patterns of pituitary gonadotropin beta-subunits (fshb and lhb), brain-type aromatase (cyp19a1b), androgen (ar1, ar2) and estrogen receptors (esr1, esr2a, esr2b), and changes in plasma steroid levels by liquid chromatography/tandem mass spectrometry in wild sablefish (Anoplopoma fimbria, order Scorpaeniformes) during a complete reproductive cycle. Transcripts for fshb increased during early gametogenesis and peaked in late vitellogenic females and late recrudescent males, while expression of lhb reached maximum levels in periovulatory and spermiating fish...
February 26, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Ketao Jin, Huanrong Lan, Junyu Zhang, Jieqing Lv, Yuan Chen, Kang Yu, Wei Wang
Purpose: To explore the prognostic value of UBASH3B in ER+ breast cancer patients and explore potential molecular mechanisms. Materials and Methods: Datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were re-analyzed to explore the association between UBASH3B and the progression of ER+ breast cancer. Kaplan-Meier plot analysis with a total of 734 ER+ samples and Gene Set Enrichment Analysis with 632 samples were used in the study. Results: High expression of UBASH3B is negatively correlated with distant metastasis free survival (DMFS, P = 0...
February 2, 2018: Oncotarget
Ke Zhang, Xiangjun Kong, Guangde Feng, Wei Xiang, Long Chen, Fang Yang, Chunyu Cao, Yifei Ding, Hang Chen, Mingxing Chu, Pingqing Wang, Baoyun Zhang
BACKGROUND: Ovarian cancer is a leading cause of the death from gynecologic malignancies. Hypoxia is closely related to the malignant growth of cells. However, the molecular mechanism of hypoxia-regulated ovarian cancer cells remains unclear. Thus, this study was conducted to identify the key genes and pathways implicated in the regulation of hypoxia by bioinformatics analysis. METHODS: Using the datasets of GSE53012 downloaded from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were screened by comparing the RNA expression from cycling hypoxia group, chronic hypoxia group, and control group...
February 26, 2018: Journal of Ovarian Research
Limei Zhang, Vito S Hernández, Jerome D Swinny, Anil K Verma, Torsten Giesecke, Andrew C Emery, Kerim Mutig, Luis M Garcia-Segura, Lee E Eiden
The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2...
February 26, 2018: Translational Psychiatry
Ilda P Ribeiro, Joana M Rodrigues, Alexandra Mascarenhas, Nadezda Kosyakova, Francisco Caramelo, Thomas Liehr, Joana B Melo, Isabel M Carreira
Oral carcinoma develops from squamous epithelial cells by the acquisition of multiple (epi) genetic alterations that target different genes and molecular pathways. Herein, we performed a comprehensive genomic and epigenetic characterization of the HSC-3 cell line through karyotyping, multicolor fluorescence in situ hybridization, array comparative genomic hybridization, and methylation-specific multiplex ligation-dependent probe amplification. HSC-3 turned out to be a near-triploid cell line with a modal number of 61 chromosomes...
February 26, 2018: Journal of Oral Science
M C Kriegmair, R M Wirtz, T S Worst, J Breyer, M Ritter, B Keck, C Boehmer, W Otto, M Eckstein, C A Weis, A Hartmann, C Bolenz, P Erben
INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed...
February 22, 2018: Translational Oncology
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