MiRNA expression profiles of primary ER-positive breast tumors following Tamoxifen treatment
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE46823 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA202408
REPOSITORIES: GEO
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Project description:Adjuvant tamoxifen is a valid treatment option for women with estrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response. We performed a global microRNA screen in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence. Patients were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005. Total RNA from FFPE tissue from 12 postmenopausal patients with ER-positive breast cancer (6 patients with and 6 patients without recurrence) was extracted. Hybridisation of biotin-labelled RNA was performed on Affymetrix GeneChip miRNA_2.0 Arrays.
2014-07-01 | E-GEOD-46823 | biostudies-arrayexpress
Project description:Purpose: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Experimental design: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by 2 independent test sets (N=60 and N=40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
2012-04-19 | GSE37405 | GEO
Project description:dataset of 60 patients with ER-positive primary breast cancer and treated with tamoxifen monotherapy for 5 years. Data were generated from LCMed cancer cells. Sample_keyword: breast cancer, tamoxifen, recurrence Keywords: other
2004-06-07 | GSE1378 | GEO
Project description:dataset of 60 patients with ER-positive primary breast cancer and treated with tamoxifen monotherapy for 5 years. Data were generated from whole tissue sections of breast cancers. Sample_keyword: breast cancer, tamoxifen, recurrence Keywords: other
2004-06-07 | GSE1379 | GEO
Project description:Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer. However, about 30% of such patients receiving tamoxifen as an adjuvant therapy experience recurrence within 15 years, and most patients with advanced disease eventually develop resistance to tamoxifen. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant human breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive MCF-7/S0.5 cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all TamRs using both sequencing and LNA-based quantitative PCR technologies. ER+ and tamoxifen sensitive breast cancer cell line (MCF-7/S0.5) and its derived tamoxifen resistant clones: TAMR-1, TAMR-4 and TAMR-8 were miRNA expression profiled in triplicates of each using Exiqon's miRCURY LNA based microRNA Ready-to-use PCR, Human panel I+II, V2.R (Exiqon, product number 203608).
2015-08-01 | E-GEOD-56411 | biostudies-arrayexpress
Project description:Endocrine resistance in breast cancer is a major clinical problem with poorly understood mechanisms. Mass spectrometry-based proteomics of a clinically-relevant tamoxifen-resistant cell line model identified increased levels of minichromosome maintenance proteins (MCM), including MCM3, as central in cell cycle and DNA replication protein-protein interaction networks associated with tamoxifen resistance. Lowering MCM3 protein expression in tamoxifen-resistant cells restored tamoxifen sensitivity and altered phosphorylation of several cell cycle regulators, such as p53(Ser315, 33), CHK1(Ser317) and cdc25b(Ser323), suggesting that MCM3 activation of important cell cycle-associated proteins overcomes tamoxifen’s anti-proliferative effects. High MCM3 expression in primary tumor tissue from two independent cohorts of ER+ breast cancer patients receiving adjuvant tamoxifen mono-therapy was an independent prognostic marker significantly associated with a shorter recurrence-free survival.
2022-02-22 | PXD001087 | Pride
Project description:Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer. However, about 30% of such patients receiving tamoxifen as an adjuvant therapy experience recurrence within 15 years, and most patients with advanced disease eventually develop resistance to tamoxifen. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant human breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive MCF-7/S0.5 cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all TamRs using both sequencing and LNA-based quantitative PCR technologies.
2015-08-01 | GSE56411 | GEO
Project description:Background MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were stably detected in blood. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers. Methods We compared levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling. We validated the level of microRNAs by real-time quantitative polymerase cycle reaction (RT-qPCR) in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Background MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were stably detected in blood. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers. Methods We compared levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling. We validated the level of microRNAs by real-time quantitative polymerase cycle reaction (RT-qPCR) in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Controls: 5 cases; ER +/HER2- breast cancer patients : 11 cases
2013-12-12 | E-GEOD-53179 | biostudies-arrayexpress
Project description:Basal expression profiling was performed to understand molecualr pathways specifically altered in tamoxifen-resistant cells. Tamoxifen is the most accepted targeted agent for treating patients with estrogen receptor (ER)-positive breast cancer (BC), but its efficacy has been limited due to drug resistance, manifested as disease recurrence and eventually death. Metabolic reprogramming of lipids has recently been recognized as a new mode of therapeutic resistance in various cancers. Therefore, we investigated previously unrecognized perturbations in lipid metabolism in tamoxifen-resistant BC by conducting comprehensive metabolomics and transcriptomics analysis.
2023-12-31 | GSE221439 | GEO
Project description:Background: Up to 40% of patients with estrogen receptor positive (ER+) breast cancer experience treatment resistance and disease recurrence, often caused by the upregulation of growth factor receptors. Understanding the mechanisms of resistance, and the identification of novel therapeutic targets is, therefore, of vital importance if breast cancer prognosis is to be further improved. Fibroblast growth factor receptor 1 (FGFR1) is a potential driver of endocrine resistance; however, clinically successful attempts at targeting FGFR1 activity in breast cancer are rare and may result from an inability to correctly identify patients that could benefit from such treatment. The identification of additional genes associated with an FGFR1-mediated mechanism of resistance will provide a more precise classification scheme for FGFR1-dependency in breast cancer. Methods: Live cell imaging and RNA sequencing of ER+ breast cancer cell lines (CAMA1, T47D, tamoxifen resistant T47D) were used to investigate FGFR1-dependency in breast cancer, mechanisms of endocrine resistance and the effects of treatment with tamoxifen and erdafitinib. An FGFR1-amplified ER+ breast cancer patient-derived xenograft (PDX) model was used to assess the effects of targeting FGFR1 in vivo. Gene expression analysis of human breast cancer from The Cancer Genome Atlas (TCGA) was used for clinical validation. Results: We evaluated the effects of targeting FGFR1 in ER+/HER2- breast cancer with aberrant FGFR1 amplification and/or overexpression. We found that the FGFR tyrosine kinase inhibitor (TKI) erdafitinib inhibited cell proliferation of FGFR1-amplified CAMA1 cells in vitro. Additionally, erdafitinib significantly enhanced the anti-proliferative effect of 4-hydroxytamoxifen (4-OHT) and its anti-tumor effect was also demonstrated in vivo. Further, we demonstrated that the proliferation of FGFR1-overexpressing tamoxifen-resistant T47D (TR-T47D) cells is dependent on FGFR1 activity. Moreover, these TR-T47D cells are re-sensitized to tamoxifen upon treatment with erdafitinib. Finally, we found that upregulation of genes related to epithelial-mesenchymal-transition (EMT) correlates with FGFR1 overexpression, and is reversed by FGFR inhibition. Conclusions: In this study we demonstrated that targeting FGFR1 in ER+/HER2- breast cancer with aberrant FGFR1 activity has the potential to inhibit tumor growth and to re-sensitize resistant tumors to tamoxifen. Furthermore, we identified a functional relationship between EMT, FGFR activity and endocrine resistance in breast tumorigenesis.
2022-08-01 | GSE200029 | GEO