GICs are considered a major determinant in glioblastoma treatment failure, as they exhibit a marked resistance to radiotherapy. However, the exact mechanisms that confer this radioresistance to GICs are still not fully understood. We have performed a microarray analysis after radiation treatment of GICs and non-GICs cultures with the aim of identifying genes, pathways and transcription factors differentially expressed between these two cellular compartments.
No associated publication
Specimen part, Treatment
View SamplesEndocrine therapies targeting the proliferative effect of 17-estradiol (17E2) through estrogen receptor (ER) are the most effective systemic treatment of ER-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 ER. 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 ER 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-ER were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ER-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 ER function.
Biological reprogramming in acquired resistance to endocrine therapy of breast cancer.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Specimen part, Cell line
View SamplesFor this study we selected a gene, -synuclein (SNCA), that is consistently under-expressed in MCF7 cells and breast tumors. Following transfection with an SNCA expression construct, two stable MCF7 clones (named MCF7-SNCA #1 and 2) were selected and examined for expression differences relative to the parental MCF7 cells.
Cancer develops, progresses and responds to therapies through restricted perturbation of the protein-protein interaction network.
Specimen part, Cell line
View SamplesAnalysis of the expression profiles of MCF7 cells transduced with a control shRNA and an TSC2-targeted shRNA (leading to tuberin depletion).
Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.
Cell line
View SamplesTo identify novel therapeutic opportunities for patients with acquired resistance to endocrine treatments in breast cancer, we applied a high-throughput drug screen. The IC50 values were determined for MCF7 and MCF7-LTED cells.
VAV3 mediates resistance to breast cancer endocrine therapy.
Cell line
View SamplesInhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Specimen part
View SamplesWe obtained fibroblast cultures from fresh surgical specimen ressected from patients with primary colorectal carcinoma: normal colonic fibroblasts (NCF=9) from the normal colonic mucosa at least 5-10cm from the surgical margin, carcinoma-associated fibroblasts from the primary tumor (CAF-PT=14) and carcinoma-associated fibroblasts (CAF-LM=11) from fresh surgical specimens of liver metastases. We identified 277 probes, in common between the three types of fibroblasts, whose expression level is sequentially deregulated according to cancer progression (NCFCAF-PTCAF-LM; fold change Log2 normalized expression>1.5 in each step). Prediction Analysis of Microarrays was applied to obtain a 25-gene signature that better characterizes each fibroblast class. The signature is able to classify patients carrying primary tumors according to prognosis. This fact was exploited to obtain a 19-gene signature (from the 277 deregulated probes) predicting recurrence with high accuracy in stage II/III colorectal cancer patients. Signature validation has been carried out in two independent datasets and in a meta-cohort of 336 stage II/III patients.
No associated publication
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe generation of B cells is a complex process requiring several cellular transitions, including cell commitment and differentiation, that are tightly controlled by the action of linage-specific transcription factors. Proper transcriptional control to establish the genetic programs characteristic of each cellular stage is essential for the correct development of B lymphocytes. In fact, deregulation of these particular transcriptional programs may result in a block in B cell maturation, contributing to the development of hematological malignancies such as leukemia and lymphoma. In this experiments, We study the HDAC7 expression levels in pro-B-ALL and Burkitt lymphoma.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Cell line
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