This SuperSeries is composed of the SubSeries listed below.
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line, Treatment
View SamplesReprogramming of cancer cell metabolism toward aerobic glycolysis, i.e. the Warburg effect, is a hallmark of cancer; according to current views, the rationale for selecting such energy-inefficient metabolism is the need to increase cellular biomass to sustain production of daughter cells and proliferation. In this view, metabolic reprogramming is considered as a simple phenotypic endpoint that occurs as a consequence of signal transduction mechanisms, including oncogene-driven nutrient uptake and metabolic rewiring. A newly emerging paradigm is instead that transcriptional networks and oncogenic signaling can also be regulated downstream of metabolic pathways, that assume causative roles in controlling cancer cell behavior, above and beyond their core biochemical function. To explore possible links between glucose metabolism and nuclear gene transcription we compared immortalized mammary epithelial cells (MCF10A) and metastatic breast cancer cells (MDA-MB-231) growing in high glucose or in the presence of a widely used inhibitor of glucose uptake / glucose metabolism, 2-deoxy-glucose (2DG).
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line, Treatment
View SamplesYAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Their role in regulating gene transcription has been so far mainly investigated by overexpressing YAP1 or TAZ, while here we sought to determine which genes are regulated by endogenous levels of YAP/TAZ. To this end, we compared MCF10A cells transfected with a control non-targeting siRNA to cells transfected with two independent mixes of siRNA targeting both YAP and TAZ.
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line
View SamplesYAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Their role in regulating gene transcription has been so far mainly investigated by overexpressing YAP1 or TAZ, while here we sought to determine which genes are regulated by endogenous levels of YAP/TAZ. To this end, we compared MCF10A cells transfected with a control non-targeting siRNA to cells transfected with two independent mixes of siRNA targeting both YAP and TAZ.
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line
View SamplesMorphogenesis of the mammary gland relies on the precise developmental control of morphological elements including TEBs, ducts and lobules. In the peripubertal mammary gland, rising levels of ovarian hormones control this development through a tightly controlled genetic program where specific sets of genes are up-regulated.
In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.
Specimen part, Treatment
View SamplesVascular endothelial growth factor is a multifunctional cytokine playing important roles in angiogenesis, tumor progression and metastasis. Alternative splicing results in the production of several different isoforms of VEGF. We have previously generated human breast cancer cells overexpressing VEGF165 or VEGF189 isoforms (referred to as the V165 and V189 clones, respectively) and showed that VEGF189-transfected cells were less tumorigenic. In this study, we used bioluminescence imaging to analyze the metastasis capacity of breast cancer cell lines (MDA-MB-321) overexpressing VEGF isoforms in nude mice. V165, V189 and control cV clones were transfected with a luciferase plasmid to generate bioluminescent clones (the V165-B, V189-B and cV clones, respectively). These clones were then injected into the left heart ventricle of nude mice.
MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.
No sample metadata fields
View SamplesTGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma.
TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.
Specimen part, Treatment
View SamplesMacrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. Overall design: mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).
Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.
Cell line, Subject
View SamplesNeuroprotective therapies for retinal degeneration may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1 in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration.
Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection.
No sample metadata fields
View SamplesPatient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.
Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer.
Specimen part, Disease, Disease stage, Time
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