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ESR1 and breast

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https://www.readbyqxmd.com/read/29342211/correction-a-meta-analysis-of-the-association-between-esr1-genetic-variants-and-the-risk-of-breast-cancer
#1
Taishun Li, Jun Zhao, Jiaying Yang, Xu Ma, Qiaoyun Dai, Hao Huang, Lina Wang, Pei Liu
[This corrects the article DOI: 10.1371/journal.pone.0153314.].
2018: PloS One
https://www.readbyqxmd.com/read/29339455/high-n-acetyltransferase-1-nat1-expression-is-associated-with-estrogen-receptor-expression-in-breast-tumors-but-is-not-under-direct-regulation-by-estradiol-17beta-diol-or-dihydrotestosterone-in-breast-cancer-cells
#2
Xiaoyan Zhang, Samantha M Carlisle, Mark A Doll, Robert C G Martin, J Christopher States, Carolyn M Klinge, David W Hein
N-acetyltransferase 1 (NAT1) is an enzyme which metabolizes carcinogens suggesting a potential role in breast carcinogenesis. High NAT1 expression in breast tumors is associated with estrogen receptor α (ERα+) and the luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme activity were higher in human breast tumors with high expression of ERα/ESR1 compared to normal breast tissue. There was a strong correlation between NATb promoter and NAT1 protein expression/enzyme activity. High NAT1 expression in tumors was not due to adipocytes as evidenced by low PLIN expression...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29311117/expanded-genomic-profiling-of-circulating-tumor-cells-in-metastatic-breast-cancer-patients-to-assess-biomarker-status-and-biology-over-time
#3
Mark Jesus M Magbanua, Hope S Rugo, Denise M Wolfe, Louai Hauranieh, Ritu Roy, Praveen Pendyala, Eduardo Sosa, Janet H Scott, Jin Sun Lee, Brandelyn N Pitcher, Terry M Hyslop, William T Barry, Steven J Isakoff, Maura N Dickler, Laura J Van't Veer, John W Park
Purpose: We profiled circulating tumor cells (CTCs) patients to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC).Methods: CTCs were isolated from 105 MBC patients using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACs), 28 of whom had serial CTC analysis (74 samples, 2-5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes (n=151) and genome-wide copy number analysis by array comparative genomic hybridization (n=49)...
January 8, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29306943/clinically-observed-estrogen-receptor-alpha-mutations-within-the-ligand-binding-domain-confer-distinguishable-phenotypes
#4
Shanhang Jia, Mark T Miedel, Marilyn Ngo, Ryan Hessenius, Ning Chen, Peilu Wang, Amir Bahreini, Zheqi Li, Zhijie Ding, Tong Ying Shun, Daniel M Zuckerman, D Lansing Taylor, Shannon L Puhalla, Adrian V Lee, Steffi Oesterreich, Andrew M Stern
OBJECTIVE: Twenty to fifty percent of estrogen receptor-positive (ER+) metastatic breast cancers express mutations within the ER ligand-binding domain. While most studies focused on the constitutive ER signaling activity commonly engendered by these mutations selected during estrogen deprivation therapy, our study was aimed at investigating distinctive phenotypes conferred by different mutations within this class. METHODS: We examined the two most prevalent mutations, D538G and Y537S, employing corroborative genome-edited and lentiviral-transduced ER+ T47D cell models...
January 6, 2018: Oncology
https://www.readbyqxmd.com/read/29291017/mir-1271-inhibits-er%C3%AE-expression-and-confers-letrozole-resistance-in-breast-cancer
#5
Tao Yu, Hai-Ru Yu, Jia-Yi Sun, Zhao Zhao, Shuang Li, Xin-Feng Zhang, Zhi-Xuan Liao, Ming-Ke Cui, Juan Li, Chan Li, Qiang Zhang
Attenuation of estrogen receptor α (ERα) expression via unknown mechanism(s) is a hallmark of endocrine-resistant breast cancer (BCa) progression. Here, we report that miR-1271 was significantly down-regulated in letrozole-resistant BCa tissues and in letrozole-resistant BCa cells. miR-1271 directly targeted the chromatin of DNA damage-inducible transcript 3 (DDIT3) gene. miR-1271 expression level was inversely correlated to DDIT3 mRNA level in BCa biopsies. Form a mechanistic standpoint, reintroduction of exogenous miR-1271 could effectively restore ERα level via inhibiting DDIT3 expression, thereby potentiating letrozole sensitivity in BCa cells...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284708/esr1-methylation-a-liquid-biopsy-based-epigenetic-assay-for-the-follow-up-of-patients-with-metastatic-breast-cancer-receiving-endocrine-treatment
#6
Sofia Mastoraki, Areti Strati, Eleni Tzanikou, Maria Chimonidou, Helen Politaki, Alexandra Voutsina, Amanda Psyrri, Vasilis Georgoulias, Evi S Lianidou
PURPOSE: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of CTCs and plasma-ctDNA. ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma-ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma-ctDNA as a potential biomarker for response to everolimus/exemestane treatment. EXPERIMENTAL DESIGN: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in: a) 65 primary breast tumors (FFPEs), b) EpCAM+ CTC-fractions (122 patients and 30 healthy donors; HD), c) plasma-ctDNA (108 patients and 30HD), d) in CTCs (CellSearch®) and in paired plasma-ctDNA for 58 BrCa patients...
December 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29278880/hypermethylation-pattern-of-esr-and-pgr-genes-and-lacking-estrogen-and-progesterone-receptors-in-human-breast-cancer-tumors-er-pr-subtypes
#7
Saeed Pirouzpanah, Forough-Azam Taleban, Parvin Mehdipour, Siamak Sabour, Morteza Atri
BACKGROUND: The option of endocrine therapy in breast cancer remains conventionally promising. OBJECTIVE: We aimed to investigate how accurately the pattern of hypermethylation at estrogen receptor (ESR) and progesterone receptor (PgR) genes may associate with relative expression and protein status of ER, PR and the combinative phenotype of ER/PR. METHODS: In this consecutive case-series, we enrolled 139 primary diagnosed breast cancer. Methylation specific PCR was used to assess the methylation status (individual test)...
December 15, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29276409/expression-profile-analysis-of-long-noncoding-rna-in-er-positive-subtype-breast-cancer-using-microarray-technique-and-bioinformatics
#8
Jing Peng, Lei Zhang, Chenwei Yuan, Liheng Zhou, Shuguang Xu, Yanping Lin, Jie Zhang, Wenjin Yin, Jinsong Lu
Background: The estrogen receptor (ER)-positive subtype of breast cancer (BC) is the most common type of BC. A number of long noncoding RNAs (lncRNAs) play critical roles in cancer biology, including BC. Previous lncRNA profiling studies have focused only on triple-negative BC and HER 2-positive BC, and no studies have specifically focused on lncRNAs in ER-positive BC. In this study, we analyzed the expression profile of the lncRNAs and mRNAs found in this particular subtype of BC for the first time...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29248526/significant-alterations-of-the-novel-15-gene-signature-identified-from-macrophage-tumor-interactions-in-breast-cancer
#9
Rajshri Singh, Priya Dagar, Shyama Pal, Bhakti Basu, Bhavani S Shankar
BACKGROUND: Tumor microenvironment is composed of a largely altered extracellular matrix with different cell types. The complex interplay between macrophages and tumor cells through several soluble factors and signaling is an important factor in breast cancer progression. METHODS: We have extended our earlier studies on monocyte and macrophage conditioned medium (MϕCM) and have carried out proteomic analysis to identify its constituents as well as validation. The 8- gene signature identified through macrophage-breast cancer cell interactions was queried in cBioportal for bioinformatic analyses...
December 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29242214/expressed-gene-fusions-as-frequent-drivers-of-poor-outcomes-in-hormone-receptor-positive-breast-cancer
#10
Karina J Matissek, Maristela L Onozato, Sheng Sun, Zongli Zheng, Andrew Schultz, Jesse Lee, Kristofer Patel, Piiha-Lotta Jerevall, Srinivas V Saladi, Allison MacLeay, Mehrad Tavallai, Tanja Badovinac-Crnjevic, Carlos Barrios, Nuran Beşe, Arlene Chan, Yanin Chavarri-Guerra, Marcio Debiasi, Elif Demirdogen, Unal Egeli, Sehsuvar Gökgöz, Henry Gomez, Pedro Liedke, Ismet Tasdelen, Sahsine Tolunay, Gustavo Werutsky, Jessica St Louis, Nora Horick, Dianne M Finkelstein, Long Phi Le, Aditya Bardia, Paul E Goss, Dennis C Sgroi, A John Iafrate, Leif W Ellisen
We sought to uncover novel genetic drivers of hormone-receptor positive (HR+) breast cancer, employing a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes including PIK3CA, AKT3, RAF1 and ESR1 in 14% (24/173) of unselected patients with advanced HR+ breast cancer. Fluorescence in situ hybridization (FISH) confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors...
December 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29234250/are-we-ready-to-use-esr1-mutations-in-clinical-practice
#11
REVIEW
Rinath Jeselsohn
The recurrent ligand-binding domain ESR1 mutations are an important mechanism of endocrine resistance in estrogen receptor-positive (ER+) metastatic breast cancer. These mutations evolve under the selective pressure of endocrine treatments and are rarely found in treatment-naïve ER+ breast cancers. Preclinical studies showed that these mutations lead to ligand-independent activity facilitating resistance to aromatase inhibitors and relative resistance to tamoxifen and fulvestrant. Retrospective analyses of ESR1 mutations in baseline plasma circulating tumor DNA from clinical trials suggest that these mutations are prognostic of poor overall survival and predictive of resistance to aromatase inhibitors in metastatic disease...
October 2017: Breast Care
https://www.readbyqxmd.com/read/29233927/comprehensive-mutation-and-copy-number-profiling-in-archived-circulating-breast-cancer-tumor-cells-documents-heterogeneous-resistance-mechanisms
#12
Costanza Paoletti, Andi K Cani, Jose M Larios, Daniel H Hovelson, Kimberly Aung, Elizabeth P Darga, Emily M Cannell, Paul J Baratta, Chia-Jen Liu, David Chu, Maryam Yazdani, Allen R Blevins, Valeria Sero, Nahomi Tokudome, Dafydd G Thomas, Christina Gersch, Anne F Schott, Yi-Mi Wu, Robert Lonigro, Dan R Robinson, Arul M Chinnaiyan, Farideh Z Bischoff, Michael D Johnson, Ben Ho Park, Daniel F Hayes, James M Rae, Scott A Tomlins
Addressing drug resistance is a core challenge in cancer research, but the degree of heterogeneity in resistance mechanisms in cancer is unclear. In this study, we conducted next-generation sequencing (NGS) of circulating tumor cells (CTC) from patients with advanced cancer, to assess mechanisms of resistance to targeted therapy and reveal opportunities for precision medicine. Comparison of the genomic landscapes of CTC and tissue metastases is complicated by challenges in comprehensive CTC genomic profiling and paired tissue acquisition, particularly in patients who progress after targeted therapy...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228577/egr1-regulates-cellular-metabolism-and-survival-in-endocrine-resistant-breast-cancer
#13
Ayesha N Shajahan-Haq, Simina M Boca, Lu Jin, Krithika Bhuvaneshwar, Yuriy Gusev, Amrita K Cheema, Diane D Demas, Kristopher S Raghavan, Ryan Michalek, Subha Madhavan, Robert Clarke
About 70% of all breast cancers are estrogen receptor alpha positive (ER+; ESR1). Many are treated with antiestrogens. Unfortunately, de novo and acquired resistance to antiestrogens is common but the underlying mechanisms remain unclear. Since growth of cancer cells is dependent on adequate energy and metabolites, the metabolomic profile of endocrine resistant breast cancers likely contains features that are deterministic of cell fate. Thus, we integrated data from metabolomic and transcriptomic analyses of ER+ MCF7-derived breast cancer cells that are antiestrogen sensitive (LCC1) or resistant (LCC9) that resulted in a gene-metabolite network associated with EGR1 (early growth response 1)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29192207/discovery-of-naturally-occurring-esr1-mutations-in-breast-cancer-cell-lines-modelling-endocrine-resistance
#14
Lesley-Ann Martin, Ricardo Ribas, Nikiana Simigdala, Eugene Schuster, Sunil Pancholi, Tencho Tenev, Pascal Gellert, Laki Buluwela, Alison Harrod, Allan Thornhill, Joanna Nikitorowicz-Buniak, Amandeep Bhamra, Marc-Olivier Turgeon, George Poulogiannis, Qiong Gao, Vera Martins, Margaret Hills, Isaac Garcia-Murillas, Charlotte Fribbens, Neill Patani, Zheqi Li, Matthew J Sikora, Nicholas Turner, Wilbert Zwart, Steffi Oesterreich, Jason Carroll, Simak Ali, Mitch Dowsett
Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR)...
November 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/29180470/er-alpha-binding-by-transcription-factors-nfib-and-ybx1-enables-fgfr2-signalling-to-modulate-estrogen-responsiveness-in-breast-cancer
#15
Thomas M Campbell, Mauro Aa Castro, Kelin Gonçalves deOliveira, Bruce Aj Ponder, Kerstin B Meyer
Two opposing clusters of transcription factors (TF) have been associated with the differential risks of estrogen receptor positive or negative breast cancers, but the mechanisms underlying the opposing functions of the two clusters are undefined. In this study, we identified NFIB and YBX1 as novel interactors of the estrogen receptor alpha (ESR1). NFIB and YBX1 are both risk TF associated with progression of ESR1-negative disease. Notably, they both interacted with the ESR1-FOXA1 complex and inhibited the transactivational potential of ESR1...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29166868/prevalence-of-esr1-e380q-mutation-in-tumor-tissue-and-plasma-from-japanese-breast-cancer-patients
#16
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Aiko Sueta, Mai Tomiguchi, Keiichi Murakami, Yoko Omoto, Hirotaka Iwase
BACKGROUND: ESR1 mutations have attracted attention as a potentially important marker and treatment target in endocrine therapy-resistant breast cancer patients. The E380Q mutation, which is one of the ESR1 mutations, is associated with estradiol (E2) hypersensitivity, increased DNA binding to the estrogen response element, and E2-independent constitutive trans-activation activity, but its frequency in ESR1 mutations remains unknown. The present study aimed to investigate the E380Q mutation in comparison with the other representative ESR1 mutations...
November 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29157627/letrozole-may-be-a-valuable-maintenance-treatment-in-high-grade-serous-ovarian-cancer-patients
#17
V Heinzelmann-Schwarz, A Knipprath Mészaros, S Stadlmann, F Jacob, A Schoetzau, K Russell, M Friedlander, G Singer, M Vetter
OBJECTIVES: Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC). METHODS: We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n=8901) and HGSOC (n=527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n=4071)...
November 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29137354/erps294-is-a-biomarker-of-ligand-or-mutational-er%C3%AE-activation-and-a-breast-cancer-target-for-cdk2-inhibition
#18
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 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133365/pre-diagnostic-smoking-is-associated-with-binary-and-quantitative-measures-of-er-protein-and-esr1-mrna-expression-in-breast-tumors
#19
Eboneé N Butler, Jeannette T Bensen, Mengjie Chen, Kathleen Conway, David B Richardson, Xuezheng Sun, Joseph Geradts, Andrew F Olshan, Melissa A Troester
Introduction Smoking is a possible risk factor for breast cancer and has been linked to increased risk of estrogen-receptor positive (ER+) disease in some epidemiologic studies. It is unknown whether smoking has quantitative effects on ER expression. Methods We examined relationships between smoking and ER expression from tumors of 1,888 women diagnosed with invasive breast cancer from a population-based study in North Carolina. ER expression was characterized using binary (+/-) and continuous measures for ER protein, ESR1 mRNA, and a multigene luminal score (LS) that serves as a measure of estrogen signaling in breast tumors...
November 13, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29093337/bisphenol-af-as-an-inducer-of-estrogen-receptor-%C3%AE-er%C3%AE-evidence-for-anti-estrogenic-effects-at-higher-concentrations-in-human-breast-cancer-cells
#20
Hiroyuki Okazaki, Shuso Takeda, Kazuhiro Kakizoe, Aya Taniguchi, Miki Tokuyasu, Taichi Himeno, Hiroyuki Ishii, Eriko Kohro-Ikeda, Koichi Haraguchi, Kazuhito Watanabe, Hironori Aramaki
Bisphenols are endocrine disruptors that are widely found in the environment. Accumulating experimental evidence suggests an adverse interaction between bisphenols and estrogen signaling. Most studies have performed experiments that focused on estrogen receptor (ER) engagement by bisphenols. Therefore, the effects of bisphenols on the expression of ERα (ESR1) and ERβ (ESR2) remain largely unknown. In the present study, we examined the effects of four bisphenols: bisphenol A (BPA), bisphenol B (BPB), bisphenol S (BPS), and bisphenol AF (BPAF), on estrogen signaling in two human breast cancer cell lines (MCF-7 and SK-BR-3)...
2017: Biological & Pharmaceutical Bulletin
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