Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA137069 | ENA |
REPOSITORIES: ENA
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Project description:Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors, because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance. Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent. We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype. Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients. MCF7-R73 cells, a monoclonal MCF7 subline that is highly sensitive to fulvestrant-induced cytocidal activity, underwent retroviral transduction with the zinc finger transcription factor (ZF-TF) activator library or with a control plasmid encoding only the NF-kB p65 activation domain. Both populations of cells were enriched for transduced cells by selecting for growth in puromycin and for fulvestrant-resistant cells by selecting with 100 nM fulvestrant. After 6 weeks of continuous treatment with fulvestrant, hundreds of drug-resistant colonies emerged from the population of cells infected with the ZF-TF activator library. By contrast, as expected, the control MCF7cell line transduced by NF-kB p65-only underwent massive cell death resulting in the complete absence of resistant colonies. DNA encoding the zinc-finger arrays was rescued by PCR from genomic DNA of pooled fulvestrant-resistant cells. The sequences of the ZF-TFs were determined and 46 unique ZF-TF clones identified. These 46 unique ZF-TFs were re-cloned into the retroviral vector and converted into clonal virus stocks that were used to transduce MCF7-R73 cells. These 46 retrovirally transduced cell populations were then challenged with fulvestrant. As compared with the control MCF-238 cells, MCF7-R73 cells transduced with six unique ZF-TFs demonstrated survival and growth in the presence of 100nM fulvestrant.
2011-07-17 | E-GEOD-27444 | biostudies-arrayexpress
Project description:T47D and MCF7 cell lines were treated with long-term (continuous) palbociclib to induce 4 resistant cell-lines (T47D RB-, T47D CDK6H, MCF7 RB- and MCF7 PacqR). Each cell line (both parental and resistant) were then treated with DMSO (control), capivasertib monotherapy, fulvestrant monotherapy and capivasertib/fulvestrant combination. RNA data is available after each treatment and resistant cell lines additionally have RNA data available after continuous palbociclib treatment.
2023-08-14 | E-MTAB-13262 | biostudies-arrayexpress
Project description:Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7. To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment. Fulvestrant-resistant breast cancer cells MCF7-FR (originated from drug-sentitive breast cancer model cell line MCF7) were transient-transfected by antigomirs targeting miR221 or miR222 (i.e. si221, si222). All three cell lines, MCF7-FR, siR221, siRNA222 were subjected to gene expression profiling.
2011-01-29 | E-GEOD-19777 | biostudies-arrayexpress
Project description:To investigate the molecular mechanisms of resistance to ER downregulator and CDK4/6 inhibitors in ER+ breast cancer, we generated two cell lines, MCF7 and T47D, resistant to fulvestrant and abemaciclib after 6-8 months of exposure to increasing doses of the drug combination We performed gene expression profiling analysis using data obtained from RNA-seq of parental MCF7 or T47D and the respective fulvestrant and abemaciclib resistant cells
2023-06-05 | GSE227102 | GEO
Project description:To investigate the function of VGLL1 in breast cancer and its role in the resistance to endocrine therapies we generated stable MCF7 cells overexpressing VGLL1 using CRISPR/Cas9 Synergistic Activation Mediator (SAM) method (MCF7 ActCas9-VGLL1 cells). MCF7 ActCas9-VGLL1 cells were also cultured in the presence of fulvestrant 100nmM or 1µM to develop fulvestrant resistant cells (MCF7 ActCas9-VGLL1-FULVR) and RNA-seq was performed in the different cell lines.
2023-12-05 | GSE216528 | GEO
Project description:Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors, because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance. Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent. We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype. Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients.
2011-07-18 | GSE27444 | GEO
Project description:Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7. To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment.
2011-01-29 | GSE19777 | GEO
Project description:MCF7 breast cancer cell lines: drug-resistant (OHT and ICI) cell lines vs. drug-sensitive (wild type) cell lines. Assessment of association between gene expression and methylation. Two comparisons: OHT-resistant vs. wild type, and ICI-resistant vs. wild type. OHT: 4-hydroxytamoxifen ICI: fulvestrant ((ICI 182780) This submission represents the methylation component of the study.
2011-10-04 | E-GEOD-25519 | biostudies-arrayexpress
Project description:We performed RNA sequencing on T47D and MCF7 cells, both parental and abema- or abema/fulvestrant- resistant, treated with either control vehicle or 300 nM (MCF7) or 100 nM (T47D) INX-315 for 7 days
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