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ESR1 and breast

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
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
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
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
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
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
Konstantinos V Floros, Timothy L Lochmann, Bin Hu, Carles Monterrubio, Mark T Hughes, Jason D Wells, Cristina Bernadó Morales, Maninderjit S Ghotra, Carlotta Costa, Andrew J Souers, Sosipatros A Boikos, Joel D Leverson, Ming Tan, Violeta Serra, Jennifer E Koblinski, Joaquin Arribas, Aleix Prat, Laia Paré, Todd W Miller, Mikhail G Dozmorov, Hisashi Harada, Brad E Windle, Maurizio Scaltriti, Anthony C Faber
HER2 ( ERBB2 ) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR -mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment...
February 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kriti Singh, Ravi S N Munuganti, Nada Lallous, Kush Dalal, Ji Soo Yoon, Aishwariya Sharma, Takeshi Yamazaki, Artem Cherkasov, Paul S Rennie
Estrogen receptor-α positive (ERα⁺) breast cancers represent 75% of all invasive breast cancer cases, while de novo or acquired resistance to ER-directed therapy is also on the rise. Numerous factors contribute to this phenomenon including the recently-reported ESR1 gene mutations such as Y537S, which amplifies co-activator interactions with ERα and promotes constitutive activation of ERα function. Herein, we propose that direct targeting of the activation function-2 (AF2) site on ERα represents a promising alternative therapeutic strategy to overcome mutation-driven resistance in breast cancer...
February 15, 2018: International Journal of Molecular Sciences
Hui-Chen Wu, Catherine Do, Irene L Andrulis, Esther M John, Mary B Daly, Saundra S Buys, Wendy K Chung, Julia A Knight, Angela R Bradbury, Theresa H M Keegan, Lisa Schwartz, Izabela Krupska, Rachel L Miller, Regina M Santella, Benjamin Tycko, Mary Beth Terry
Family history, a well-established risk factor for breast cancer, can have both genetic and environmental contributions. Shared environment in families as well as epigenetic changes that also may be influenced by shared genetics and environment may also explain familial clustering of cancers. Epigenetic regulation, such as DNA methylation, can change the activity of a DNA segment without a change in the sequence; environmental exposures experienced across the life course can induce such changes. However, genetic-epigenetic interactions, detected as methylation quantitative trait loci (mQTLs; a...
February 13, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Danai Fimereli, Debora Fumagalli, David Brown, David Gacquer, Françoise Rothé, Roberto Salgado, Denis Larsimont, Christos Sotiriou, Vincent Detours
The advent of next generation sequencing technologies has boosted the interest in exploring the role of fusion genes in the development and progression of solid tumors. In breast cancer, most of the detected gene fusions seem to be "passenger" events while the presence of recurrent and driver fusions is still under study. We performed RNA sequencing in 55 well-characterized breast cancer samples and 10 adjacent normal breast tissues, complemented by an analysis of SNP array data. We explored the presence of fusion genes and defined their association with breast cancer subtypes, clinical-pathologic characteristics and copy number aberrations...
February 13, 2018: Genes, Chromosomes & Cancer
Xiao-Feng Lu, De Zeng, Wei-Quan Liang, Chun-Fa Chen, Shu-Ming Sun, Hao-Yu Lin
Forkhead box protein M1(FoxM1) is a member of forkhead superfamily transcription factors. Emerging evidences have progressively contributed to our understanding on a central role of FoxM1 in human cancers. However, perspectives on the function of FoxM1 in breast cancer (BC) remain conflicting, and mostly were from basic research. Here, we explored the expression profile and prognostic values of FoxM1 based on analysis of pooled clinical datasets derived from online accessible databases, including ONCOMINE , Breast Cancer Gene-Expression Miner v4...
January 2, 2018: Oncotarget
Rabeb Ghali, Maryam A Al-Mutawa, Abrar K Al-Ansari, Sonia Zaied, Hanen Bhiri, Touhami Mahjoub, Wassim Y Almawi
BACKGROUND: Estrogen is key to breast cancer pathogenesis, and acts by binding its receptor (ER), which exists as ERα and ERβ, encoded by ESR1 and ESR2 genes, respectively. Studies that investigated the association of ESR1 and ESR2 variants with breast cancer yielded mixed outcome, and ethnic contribution was proposed. We evaluated the association between ESR1 and ESR2 variants and breast cancer and associated features in Tunisian women. METHODS: Retrospective case-control study involving 207 female breast cancer patients, and 284 control women...
February 4, 2018: Gene
Min-Ae Song, Theodore M Brasky, Daniel Y Weng, Joseph P McElroy, Catalin Marian, Michael J Higgins, Christine Ambrosone, Scott L Spear, Adana A Llanos, Bhaskar V S Kallakury, Jo L Freudenheim, Peter G Shields
Despite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAm's. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA-BRCA data were used for replication...
December 29, 2017: Oncotarget
Andrea Friesenhengst, Tamara Pribitzer-Winner, Heidi Miedl, Katharina Pröstling, Martin Schreiber
Genetic variants in CYP19A1, the gene encoding aromatase, have been reported to be associated with circulating estrogen concentrations, a key risk factor for breast cancer. The mechanism underlying this association is still unclear; it has been suggested that some of these variants may alter the expression and/or activity of aromatase. Here we analyzed the expression of intra-tumoral CYP19A1 messenger RNA (mRNA) and the genotypes of rs10046, a well-characterized single nucleotide polymorphism in CYP19A1, in 138 breast cancer patients and 15 breast cancer cell lines...
January 23, 2018: Hormones & Cancer
R J Hartmaier, S E Trabucco, N Priedigkeit, J H Chung, C A Parachoniak, P Vanden Borre, S Morley, M Rosenzweig, L M Gay, M E Goldberg, J Suh, S Ali, J Ross, B Leyland-Jones, B Young, C Williams, B Park, M Tsai, B Haley, J Peguero, R D Callahan, I Sachelarie, J Cho, J M Atkinson, A Bahreini, A M Nagle, S L Puhalla, R J Watters, Z Erdogan-Yildirim, L Cao, S Oesterreich, A Mathew, P C Lucas, N E Davidson, A M Brufsky, G M Frampton, P J Stephens, J Chmielecki, A V Lee
Background: ER-positive metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods: To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (1) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (2) high coverage (>500x) comprehensive genomic profiling of 287-395 cancer-related genes across 9,542 solid tumors (5,216 from metastatic disease), and (3) ultra-high coverage (>5,000x) genomic profiling of 62 cancer-related genes in 254 ctDNA samples...
January 19, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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
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
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
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
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
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