Expression data from MCF7 and MCF7-LTED cells treated with YC-1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38829 | GEO | 2014/03/17
SECONDARY ACCESSION(S): PRJNA169021
REPOSITORIES: GEO
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Project description:To identify novel therapeutic opportunities for patients with acquired resistance to endocrine treatments in breast cancer, we applied high-throughput screening to explore currently marketed drugs. The Ec50 values were determined for MCF7 and LTED cell lines to identify the compounds showing higher inhibition of LTED cells. The best compound was YC-1 and gene microarray studies were done in vitro for mechanistic exploration. MCF7 and LTED cells were treated with YC-1 for RNA extraction and hybridization on Affymetrix microarrays.
2014-03-17 | E-GEOD-38829 | biostudies-arrayexpress
Project description:Wild type (wt) MCF7 cells, modelling breast cancer at primary diagnosis, were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol (E2). Long-term oestrogen deprived (LTED) cell lines, which model resistance to endocrine therapy, were cultured in phenol red-free RPMI in the absence of exogenous E2 and supplemented with 10% dextran charcoal-stripped bovine serum (DCC). Samples were harvested at baseline and at the point of resistance (LTED). In order to do comparative analysis in the ER-interactome of wt-MCF7 and MCF7-LTED cells, ER-RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) was conducted in these cells.
2020-07-13 | PXD004648 | Pride
Project description:Wild type (wt) MCF7 cells, modelling breast cancer at primary diagnosis, were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol (E2). Long-term oestrogen deprived (LTED) cell lines, which model resistance to endocrine therapy, were cultured in phenol red-free RPMI in the absence of exogenous E2 and supplemented with 10% dextran charcoal-stripped bovine serum (DCC). Samples were harvested at baseline and at the point of resistance (LTED). To reveal differential protein abundances between wt-MCF7 and MCF7 LTED, the peptides were labelled with chemical labelling and underwent fractionation using OFFGEL electrophoresis.
2016-06-01 | PXD004085 | Pride
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: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.
2010-09-01 | GSE20361 | GEO
Project description: Not available
| S-ECPF-GEOD-38829 | biostudies-other
Project description:Wild type (wt) SUM44 cells, modelling breast cancer at primary diagnosis, were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol (E2). Long-term oestrogen deprived (LTED) cell lines, which model resistance to endocrine therapy, were cultured in phenol red-free RPMI in the absence of exogenous E2 and supplemented with 10% dextran charcoal-stripped bovine serum (DCC). Samples were harvested at baseline and at the point of resistance (LTED). To reveal differential protein abundances between wt-SUM44 and SUM44-LTED, the peptides were labelled with dimethyl labelling and underwent fractionation using OFFGEL electrophoresis. In order to reveal the ER-interactome, RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) was conducted in wt-SUM44 and SUM44-LTED.
2017-12-11 | PXD004807 | Pride
Project description:To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. This SuperSeries is composed of the SubSeries listed below.
2008-12-01 | GSE8141 | GEO
Project description:Background: Invasive lobular breast carcinoma (ILC) is a histological subtype of breast cancer that is characterized by loss of E-cadherin, and high expression of estrogen receptor alpha (ER). Many patients with ILC are effectively treated with adjuvant aromatase inhibitors (AIs), however, acquired AI resistance remains a significant problem. Methods: To identify underlying mechanisms of acquired antiestrogen resistance in ILC, we developed a total of 6 long-term estrogen-deprived (LTED) variant cell lines of the human ILC cell lines SUM44PE (SUM44; 2 lines) and MDA-MB-134VI (MM134; 4 lines). To better understand mechanisms of AI resistance in these models, we performed transcriptional profiling analysis by RNA-sequencing. Results: MM134 LTED cells expressed ER at decreased level and lost growth response to estradiol, while SUM44 LTED cells retained partial ER activity. Our transcriptional profiling analysis identified shared activation of lipid metabolism across all 6 independent models. However, the underlying basis of this signature was distinct between models. Oxysterols were able to promote the proliferation of SUM44 LTED cells, but not MM134 LTED. In contrast, MM134 LTED cells displayed high expression of the Sterol regulatory element-binding protein 1 (SREBP1), a regulator of fatty acid and cholesterol synthesis, and were hypersensitive to genetic or pharmacological inhibition of SREBPs. Several SREBP1 downstream targets involved in fatty acid synthesis, including FASN, were induced, and MM134 LTED cells were more sensitive to etomoxir, an inhibitor of the rate-limiting enzyme in β-oxidation, than their respective parental control cells. Conclusions: Our characterization of a unique series of AI-resistant ILC models identifies a lipogenic phenotype, including overexpression of SREBP1. This novel metabolic target deserves further study for the prevention and treatment of AI-resistance for patients with ILC.
2018-08-30 | GSE116744 | GEO
Project description:MCF7 and BT474 cell lines were exposed to LTED culture for 0 and 2 days, 6 weeks and 10 months and monitored for changes in gene expression
2013-10-02 | GSE50820 | GEO