Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA187554 | ENA |
REPOSITORIES: ENA
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Project description:Since differential miRNA expression patterns associated with acquired AI resistance have been poorly investigated, the aim of this study was to delineate the deregulation of miRNA expression associated with letrozole response failure in a new model of letrozole resistance. For this purpose, we generated and characterized a novel cellular model of acquired resistance to letrozole (Res-Let cells) and performed microarray experiments to identify miRNAs whose expression was either deregulated between control (MCF-7aro) and resistant cells (Res-Let) or differentially expressed between the two cell lines under letrozole exposure. With the aim to select relevant miRNAs, two independent cell culture replicates were performed for each experimental condition. MCF-7aro and Res-Let cells were grown in the presence of androstenedione (AD) combined or not with letrozole. Two independent cell culture replicates for each experimental condition were used to generate total RNA. Total RNA was extracted from cell culture using a Qiagen RNA extraction kit and RNA quality was assessed using the BioAnalyzer 2100M-bM-^DM-" (Agilent Technologies). Complex probes were produced from these RNA, then hybridized to GeneChipM-BM-. miRNA 3.0 array according to the manufacturer's recommendations (Affymetrix).
2013-01-30 | E-GEOD-43766 | biostudies-arrayexpress
Project description:Since differential miRNA expression patterns associated with acquired AI resistance have been poorly investigated, the aim of this study was to delineate the deregulation of miRNA expression associated with aromatase inhibitor (AI) response failure in new cellular models of AI resistance. For this purpose, we generated and characterized novel cellular models of acquired resistance to letrozole (Res-Let cells) and to anastrozole (Res-Ana cells) and performed microarray experiments to identify miRNAs whose expression was either deregulated between control (MCF-7aro) and resistant cells (Res-Let or Res-Ana). With the aim to select relevant miRNAs, two independent cell culture replicates were performed for each experimental condition.
2013-01-30 | GSE43766 | GEO
Project description:Acquired resistance to aromatase inhibitor (AI) therapy is a major clinical problem in the treatment of breast cancer. The detailed mechanisms of how tumour cells develop this resistance remain unclear. Here estrogen receptor ChIPseq analysis identifies adaptations of the ER in response to prolonged letrozole treatment.
2016-03-21 | GSE54592 | GEO
Project description:We performed ChIP-seq on MCF7 cells in an effort to discern differential binding patterns between wild type MCF7s and MCF7s that have acquired resistance to Tamoxifen and Estrogen deprivation. Furthermore, we also performed an HAtag ChIP on a DOX inducible RUNX2 overexpression MCF7 cell line. We also performed RNA-seq on MCF7 cells to determine transciptional changes after acquisition of Tamoxifen resistance, and also transciptional changes in a DOX inducible RUNX2 overexpression model.
2017-03-01 | GSE86538 | GEO
Project description:Endocrine therapies targeting the proliferative effect of 17β-estradiol (17βE2) through estrogen receptor α (ERα) are the most effective systemic treatment of ERα-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through a molecular mechanism that is not yet fully understood. The long-term estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors (AIs) in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERα. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were influenced by transcription factors known to be involved in acquired resistance or cell proliferation (e.g. IRF1 and E2F1, respectively) but, notably, not by canonical ERα transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)- to pS167-ERα were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERα-negative status, early response to letrozole and recurrence after tamoxifen treatment. This study proposes a mechanism for acquired resistance to estrogen deprivation that is coordinated across biological levels and independent of canonical ERα function. LTED (long term estrogen deprived) cell line was generated from MCF-7 cells by long-term culture under estrogen deprivated conditions. And RNA samples were obtained after 3, 15, 30, 90, 120, 150 and 180 days.
2010-09-01 | E-GEOD-20361 | biostudies-arrayexpress
Project description:Resistance to endocrine therapy agents has presented a clinical obstacle in the treatment of hormone-dependent breast cancer. Our laboratory has initiated a study of microRNA regulation of signaling pathways that may result in breast cancer progression on aromatase inhibitors (AI). Microarray analysis of microRNA expression identified 115 significantly regulated microRNAs, of which 49 microRNAs were believed to be hormone-responsive. Within the AI-resistant cells, microRNAs were differentially expressed between the steroidal and non-steroidal AI-resistant lines. Also, a group of microRNAs were inversely expressed in the AI-resistant lines versus LTEDaro and tamoxifen-resistant. We focused our work on hsa-miR-128a which was hormone-responsive and up-regulated in the letrozole-resistant cell lines. Human miR-128a was shown to negatively target TGFBRI protein expression by binding to the 3âUTR region of the gene. Loss of TGFBRI resulted in compromised sensitivity to the growth inhibitory effects of TGFB in the letrozole-resistant lines. Inhibition of endogenous miR-128a resulted in re-sensitization of the letrozole-resistant lines to TGFB growth inhibitory effects. This data suggests that the hormone-responsive miR-128a can modulate TGFB signaling and survival of the letrozole-resistant cell lines. To our knowledge, this is the first study to address the role of microRNA regulation as well as TGFB signaling in AI-resistant breast cancer cell lines. We believe that in addition to estrogen-modulation of gene expression, hormone-regulated microRNAs may provide an additional level of post-transcriptional regulation of signaling pathways critically involved in breast cancer progression and AI-resistance. To look at microRNA expression profiles of breast cancer cell lines derived from MCF-7 cells that are resistant to endocrine therapy agents. MCF-7 cells that overexpress aromatase (MCF-7aro) were cultured long-term in the presence of endocrine therapy agents until cells acquired resistance. Three different aromatase inhibitors (letrozole, anastrozole or exemestane) were used, as well as the ER antagonist tamoxifen, or the hormone-free long-term estrogen deprived cells (LTED). Three replicates of the control cells (MCF-7aro) and all resistant cells were used for microarray experiments. Total of 23 samples were analyzed by microarray.
2010-05-16 | E-GEOD-17775 | biostudies-arrayexpress
Project description:Molecular mechanisms underlying the development of resistance to platinum treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing identification of factors that are regulated during initial treatment and of acquired resistance-related genes. In this study, we used whole genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its cisplatin-resistant variant A2780cis, before and after carboplatin treatment in vivo.
2013-10-01 | E-MTAB-1858 | biostudies-arrayexpress
Project description:Treatment with ALK tyrosine kinase inhibitors often elicits profound initial antitumor responses in ALK fusion-positive patients with lung adenocarcinoma. However, patients invariably develop acquired resistance to ALK inhibitors. In this study, we aimed to identify molecular events that limit the response to ALK inhibition using genetic and epigenetic approaches. To identify novel mechanisms of acquired resistance to ALK inhibitors, we established in vitro models of acquired resistance to ceritinib using H3122 cell. For in vitro model, H3122 parental cells, ceritinib-treated resistant cells, and non-resistant cells that combinely treated with certinib and panobinostat were used for small RNA-seq based miRNA expression profiling.
2018-05-28 | GSE81486 | GEO
Project description:Deacetylation of miRNA-34a and miRNA-449 induces epithelial-mesenchymal transition and acquired resistance to ALK inhibitors
| PRJNA382553 | ENA