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ESR1 and breast

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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/29063679/estrogen-receptor-mutations-and-splice-variants-determined-in-liquid-biopsies-from-metastatic-breast-cancer-patients
#4
Nick Beije, Anieta M Sieuwerts, Jaco Kraan, Ngoc M Van, Onstenk Wendy, Silvia R Vitale, Michelle van der Vlugt-Daane, Luc Y Dirix, Anja Brouwer, Paul Hamberg, Felix E de Jongh, Agnes Jager, Caroline M Seynaeve, Maurice P H M Jansen, John A Foekens, John W M Martens, Stefan Sleijfer
Mutations and splice variants in the estrogen receptor (ER) gene, ESR1, may yield endocrine resistance in metastatic breast cancer (MBC) patients. These putative endocrine resistance markers are likely to emerge during treatment and therefore its detection in liquid biopsies, such as circulating tumor cells (CTCs) and cell-free DNA (cfDNA), is of great interest. This research aimed to determine if ESR1 mutations and splice variants occur more frequently in CTCs of MBC patients progressing on endocrine treatment...
October 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29045530/tracking-evolution-of-aromatase-inhibitor-resistance-with-circulating-tumour-dna-analysis-in-metastatic-breast-cancer
#5
Charlotte Fribbens, Isaac Garcia Murillas, Matthew Beaney, Sarah Hrebien, Ben O'Leary, Lucy Kilburn, Karen Howarth, Michael Epstein, Emma Green, Nitzan Rosenfeld, Alistair Ring, Stephen Johnston, Nicholas Turner
Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and Methods: 83 patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study...
October 4, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29032804/-clinical-relevance-of-esr1-circulating-mutations-detection-in-hormone-receptor-positive-metastatic-breast-cancer
#6
REVIEW
Florian Clatot, Anne Perdrix, David Sefrioui, Nasrin Sarafan-Vasseur, Frédéric Di Fiore
If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials...
October 9, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29029469/genetic-and-environmental-factors-and-serum-hormones-and-risk-of-estrogen-receptor-positive-breast-cancer-in-pre-and-postmenopausal-japanese-women
#7
Jiazhi Guo, Aiko Sueta, Koshi Nakamura, Nobuyasu Yoshimoto, Motoi Baba, Naoko Ishida, Kanako Hagio, Tatsuya Toyama, Hirotaka Iwase, Akiko Tamakoshi, Hiroko Yamashita
Breast cancer incidence in Japanese women has more than tripled over the past two decades. We have previously shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive, HER2-negative subtype. We conducted a case-control study; ER-positive, HER2-negative breast cancer patients who were diagnosed since 2011 and women without disease were recruited. Environmental factors, serum levels of testosterone and 25-hydroxyvitamin D, and common genetic variants reported as predictors of ER-positive breast cancer or found in Asian women were evaluated between patients and controls in pre- and postmenopausal women...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029116/upregulation-of-irs1-enhances-igf1-response-in-y537s-and-d538g-esr1-mutant-breast-cancer-cells
#8
Zheqi Li, Kevin M Levine, Amir Bahreini, Peilu Wang, David Chu, Ben Ho Park, Steffi Oesterreich, Adrian V Lee
Increased evidence suggests that somatic mutations in the ligand binding domain of estrogen receptor (ERα/ESR1) are critical mediators of endocrine-resistant breast cancer progression. Insulin-like growth factor-1 (IGF1) is an essential regulator of breast development and tumorigenesis, and also has a role in endocrine resistance. A recent study showed enhanced crosstalk between IGF1 and ERα in ESR1 mutant cells, but detailed mechanisms are incompletely understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and D538G ESR1 mutations, we characterized altered IGF1 signaling...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/29021233/divergent-activity-of-pseudogene-ptenp1-in-er-positive-and-negative-breast-cancer
#9
Synnøve Yndestad, Eilin Austreid, Kai Ove Skaftnesmo, Per Eystein Lønning, Hans P Eikesdal
Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to adsorb microRNAs (miRs) targeting the PTEN tumor suppressor for degradation, and PTENP1 upregulation is known to inhibit growth in preclinical cancer models. Here, PTENP1 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and negative breast cancer cells. PTENP1 upregulation decreases PTEN gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth in vivo...
October 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28984209/genome-wide-identification-of-key-modulators-of-gene-gene-interaction-networks-in-breast-cancer
#10
Yu-Chiao Chiu, Li-Ju Wang, Tzu-Hung Hsiao, Eric Y Chuang, Yidong Chen
BACKGROUND: With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer...
October 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28978063/predictive-value-of-molecular-subtyping-in-nmibc-by-rt-qpcr-of-erbb2-esr1-pgr-and-mki67-from-formalin-fixed-tur-biopsies
#11
Johannes Breyer, Ralph Markus Wirtz, Wolfgang Otto, Mark Laible, Kornelia Schlombs, Philipp Erben, Maximilian Christian Kriegmair, Robert Stoehr, Sebastian Eidt, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978004/detection-of-esr1-mutations-in-circulating-cell-free-dna-from-patients-with-metastatic-breast-cancer-treated-with-palbociclib-and-letrozole
#12
Rekha Gyanchandani, Karthik J Kota, Amruth R Jonnalagadda, Tanya Minteer, Beth A Knapick, Steffi Oesterreich, Adam M Brufsky, Adrian V Lee, Shannon L Puhalla
ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974548/selective-androgen-receptor-modulator-rad140-inhibits-the-growth-of-androgen-estrogen-receptor-positive-breast-cancer-models-with-a-distinct-mechanism-of-action
#13
Ziyang Yu, Suqin He, Dannie Wang, Hitisha K Patel, Chris P Miller, Jeff Brown, Gary Hattersley, Jamal C Saeh
PURPOSE: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+) breast cancer cells and were used to treat breast cancer eliciting favorable response. The present study evaluates the activity and efficacy of the oral selective AR modulator (SARM) RAD140 in in vivo and in vitro models of AR/ER+ breast cancer. EXPERIMENTAL DESIGN: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity...
October 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28973975/identification-of-linkages-between-edcs-in-personal-care-products-and-breast-cancer-through-data-integration-combined-with-gene-network-analysis
#14
Hyeri Jeong, Jongwoon Kim, Youngjun Kim
Approximately 1000 chemicals have been reported to possibly have endocrine disrupting effects, some of which are used in consumer products, such as personal care products (PCPs) and cosmetics. We conducted data integration combined with gene network analysis to: (i) identify causal molecular mechanisms between endocrine disrupting chemicals (EDCs) used in PCPs and breast cancer; and (ii) screen candidate EDCs associated with breast cancer. Among EDCs used in PCPs, four EDCs having correlation with breast cancer were selected, and we curated 27 common interacting genes between those EDCs and breast cancer to perform the gene network analysis...
September 30, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28970855/nanostring-ncounter%C3%A2-approach-in-breast-cancer-a-comparative-analysis-with-quantitative-real-time-polymerase-chain-reaction-in-situ-hybridization-and-immunohistochemistry
#15
Jiyeon Hyeon, Soo Youn Cho, Min Eui Hong, So Young Kang, Ingu Do, Young Hyuck Im, Eun Yoon Cho
PURPOSE: Accurate testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is essential for breast cancer treatment. At present, immunohistochemistry (IHC)/florescence in situ hybridization (FISH) are widely accepted as the standard testing methods. To investigate the value of NanoString nCounter®, we performed its comparative analysis with IHC/FISH and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the assessment of ER, PR, and HER2...
September 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28956815/barhl1-is-downregulated-in-alzheimer-s-disease-and-may-regulate-cognitive-functions-through-esr1-and-multiple-pathways
#16
Debmalya Barh, María E García-Solano, Sandeep Tiwari, Antaripa Bhattacharya, Neha Jain, Daniel Torres-Moreno, Belén Ferri, Artur Silva, Vasco Azevedo, Preetam Ghosh, Kenneth Blum, Pablo Conesa-Zamora, George Perry
The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue microarray (TMA), we report for the first time that BARHL1 is downregulated in hormone-negative breast cancers and Alzheimer's disease (AD). Furthermore, using an integrative bioinformatics approach and mining knockout mouse data, we show that: (i) BARHL1 and Estrogen Receptor 1 (ESR1) may constitute a network that regulates Neurotrophin 3 (NTF3)- and Brain Derived Neurotrophic Factor (BDNF)-mediated neurogenesis and neural survival; (ii) this is probably linked to AD pathways affecting aberrant post-translational modifications including SUMOylation and ubiquitination; (iii) the BARHL1-ESR1 network possibly regulates β-amyloid metabolism and memory; and (iv) hsa-mir-18a, having common key targets in the BARHL1-ESR1 network and AD pathway, may modulate neuron death, reduce β-amyloid processing and might also be involved in hearing and cognitive decline associated with AD...
September 28, 2017: Genes
https://www.readbyqxmd.com/read/28945887/hybrid-capture-based-genomic-profiling-of-circulating-tumor-dna-from-patients-with-estrogen-receptor-positive-metastatic-breast-cancer
#17
J H Chung, D Pavlick, R Hartmaier, A B Schrock, L Young, B Forcier, P Ye, M K Levin, M Goldberg, H Burris, L M Gay, A D Hoffman, P J Stephens, G M Frampton, D M Lipson, D M Nguyen, S Ganesan, B H Park, L T Vahdat, B Leyland-Jones, T I Mughal, L Pusztai, J O'Shaughnessy, V A Miller, J S Ross, S M Ali
Background: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28945747/establishment-of-primary-mixed-cell-cultures-from-spontaneous-canine-mammary-tumors-characterization-of-classic-and-new-cancer-associated-molecules
#18
Luciana B Gentile, Marcia K Nagamine, Luiz R Biondi, Daniel S Sanches, Fábio Toyota, Tatiane M Giovani, Isis P de Jesus, Ivone I M da Fonseca, Nicolle Queiroz-Hazarbassanov, Bruno L Diaz, Cristina de O Massoco Salles Gomes, Maria Lucia Z Dagli
There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28924522/estradiol-as-a-targeted-late-line-therapy-in-metastatic-breast-cancer-with-estrogen-receptor-amplification
#19
Karthik Kota, Adam Brufsky, Steffi Oesterreich, Adrian Lee
Estradiol is a major regulator of growth for the subset of breast cancers that express the estrogen receptor (ER, ESR1). Strategies to block ER action, via reduction of estradiol or direct inhibition of ER, have shown major success in the prevention and treatment of breast cancer. However, most ER-positive (ER+) metastatic breast cancers (MBC) eventually become resistant to these interventions. Interestingly, high dose estrogen can induce apoptosis in breast cancer cell lines, and high-dose estrogen has been used for over 50 years as therapy for ER+ breast cancer...
July 6, 2017: Curēus
https://www.readbyqxmd.com/read/28905136/highly-sensitive-detection-of-esr1-mutations-in-cell-free-dna-from-patients-with-metastatic-breast-cancer-using-molecular-barcode-sequencing
#20
Nanae Masunaga, Naofumi Kagara, Daisuke Motooka, Shota Nakamura, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
PURPOSE: We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). METHODS: The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR)...
September 13, 2017: Breast Cancer Research and Treatment
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