MYC threshold required to maintain tumor phenotype
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE10200 | GEO | 2008/07/01
SECONDARY ACCESSION(S): PRJNA108319
REPOSITORIES: GEO
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Project description:We demonstrate that there is a level of MYC expression that is required for maintaining a tumor phenotype and at this threshold there is a switch from a state of cellular proliferation to a state of proliferative arrest and apoptosis. We analyzed changes in gene expression by oligonucleotide microarray analysis and quantitative PCR and found significant changes (FDR=5%) in 2348 down regulated genes and 1573 upregulated genes. Critical changes in gene expression that occurred at or near the threshold level of MYC expression includes genes that have been implicated in G1/S, G2/M cell cycle checkpoint pathways and death receptor/apoptosis signaling. Keywords: Dose response - MYC inactivation by doxycycline treatment 11 samples, replicates not included
2010-05-25 | E-GEOD-10200 | biostudies-arrayexpress
Project description:In response to stress, the p53 tumor suppressor induces arrest or apoptosis by transcriptionally regulating genes that mediate these processes. It has been proposed that the levels of p53 can influence the choice between these different outcomes, but the mechanisms involved are not clear. To gain mechanistic understanding of this p53-dependent cell fate decision, we generated a p53 inducible system that allowed tight regulation of p53 expression in human mammary epithelial cells. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Using microarray and chromatin immunoprecipitation analysis, we showed that low and high levels of p53 bind to and activate the same set of pro arrest and pro apoptotic target genes, induced to lower and higher levels, respectively. We propose that the cell fate decision between arrest and apoptosis in these cells is determined by a higher threshold required for p53 dependent apoptosis. We suggest that high level p53 activation is crucial in order to achieve maximum efficacy of p53 targeted cancer therapies.
2011-07-19 | E-GEOD-30753 | biostudies-arrayexpress
Project description:Background and study aims
The NHS Bowel Cancer Screening Programme (BCSP) offers a stool test every 2 years which checks for the presence of blood as this may indicate bowel cancer or something that may develop into cancer over time. From June 2019, the BCSP began using a new stool test called FIT, which quantifies how much blood, if any, is present. If the FIT result gives a level above a certain number or threshold, the patient is referred for a more invasive examination. This threshold can be set at any level, but in general, the lower the FIT threshold, the more sensitive the test, resulting in more bowel cancers being detected. Therefore, the optimal FIT threshold must balance the benefits of detecting potential cancers early versus the risk and costs of undergoing more invasive investigations.
The main aim of this study is to determine if using a low-threshold FIT compared to the higher-threshold FIT used in the BCSP will reduce the number of bowel cancer cases. This is important because if the study shows that low-threshold FIT reduces the number of bowel cancers and subsequent deaths, and is cost-effective, a strong case could be made to lower the FIT threshold used in the BCSP. This would mean that everyone taking part in screening would benefit from a more sensitive test.
Who can participate?
Men and women aged 60-66 who are eligible for FIT screening through the English BCSP
What does the study involve?
Participants will be recruited through the BCSP and randomly allocated to either a low- or the standard higher-threshold FIT used in the BCSP. Recruited participants will complete their bowel cancer screening as normal. Over a 10-year period, the researchers will examine data from up to five FITs per person to determine how much more effective low-threshold FIT is at reducing the number of bowel cancers and subsequent deaths from this disease.
| 2423055 | ecrin-mdr-crc
Project description:Patients with epilepsy often experience increased frequency of seizures at night. Given the crucial role glial cells play in modulating neuronal excitability, we hypothesize that circadian changes in glia may affect changes in seizure threshold. Fatty acid binding protein 7 (Fabp7) is expressed in brain astrocytes and is involved in the transport of fatty acids, signal transduction, and gene transcription. Its mRNA expression levels rise and fall in a circadian rhythm and is necessary for normal sleep regulation. We examined if Fabp7 influences electrically induced seizure threshold and differential gene expression in wild type (WT) vs. Fabp7 knockout (KO) mice with and without seizure.
2024-11-06 | GSE271985 | GEO
Project description:Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals. Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as “nonsmokers,” “active smokers,” and “low exposure.” The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml. Conclusions: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low level tobacco smoke exposure to lung health risk, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke.
2011-02-02 | GSE19667 | GEO
Project description:Maturation is a critical developmental process, and the age and size at which it occurs have important fitness consequences. Maturation is also remarkably variable across species, genotypes and environments. Despite this variation, certain key mechanisms, including a minimum size or state threshold for maturation, are proposed to underlie maturation across a broad diversity of taxa. Physiological changes associated with thresholds have been elucidated in some model systems; however, there is evidence that thresholds are not fixed but developmentally plastic. In the crustacean Daphnia pulex, it is unclear whether maturation follows a threshold or is a gradual process more akin to a rate. Changes in gene expression across four instars before and during maturation were compared in a cDNA microarray experiment. In total 45 genes were significantly differentially expressed over the course of ontogeny. Among those showing higher levels of expression later in development were genes for lipid-transport proteins (six), histones (eight) and involved in RNA processing or transcription (five). Eight of the 45 genes, including several vitellogenins, showed a marked increase in expression between developmental stages, which may explain the maturation threshold previously posited in this species. However, most genes showed gradual increases or decreases in expression during the course of development, suggesting a maturation process more analogous to a rate than a discrete developmental switch.
2015-04-09 | E-MTAB-3388 | biostudies-arrayexpress
Project description:Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify miRNA-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we find that three miRNA families, miR-20, miR-92 and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the pro-apoptotic protein BIM. These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are not only primed for differentiation but also for cell death. We used microarrays to compare the gene expression profiles of Dicer conditional Epiblast stem cells (Dicer fx/fx EpiSCs, used as control cells) and Dicer deleted epiblast stem cells (Dicer-/- EpiSCs) five days after the induction of Dicer deletion
2014-09-06 | GSE61157 | GEO
Project description:Background: Many tools used to analyze microarrays in different conditions have been described. However, the integration of the deregulated genes within coherent metabolic pathways is lacking. Currently no objective selection criterion, based on biological functions exists, to determine a threshold demonstrating that a gene is indeed differentially expressed. Methodology/Principal Findings: To improve transcriptomic analysis of microarrays, we propose a new statistical approach, which takes into account biological parameters. We present an iterative method to optimise the selection of differentially expressed gene in two experimental conditions. The stringency level of gene selection was associated simultaneously with the p-value of expression variation and the occurrence rate parameter, which is associated with the percentage of donors whose transcriptomic profile is similar. Our method intertwines stringency level settings, biological data and a knowledge database to highlight molecular interactions using networks and pathways. Analysis performed during iterations helped us select the optimal threshold required for the most pertinent selection of differently expressed genes. Conclusions/significance: We have applied this approach to the well documented mechanism of human macrophage response to lipopolysaccharide stimulation. For example, we thus verified that our method was able to determine with the highest degree of accuracy the best threshold for selecting genes, which are truly differentially expressed.
2011-06-19 | GSE22858 | GEO
Project description:One aspect of intra-tumoral heterogeneity in glioblastoma involves subpopulations of cells capable of self-renewal and indefinite propagation. Conceptually, this capacity is frequently treated as a static property. Here we provide data suggesting that tumorigenicity in glioblastomais a dynamic property that can be acquired or lost. Integrated expression analyses suggest that tumorigenicity is determined by the level of MYC expression relative to a threshold. Transitions between tumorigenic and non-tumorigenic cell states are associated with changes in histone modifications at the MYC locus, suggesting tumorigenicity is epigenetically regulated.
2014-03-28 | GSE56316 | GEO
Project description:Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals. Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as “nonsmokers,” “active smokers,” and “low exposure.” The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml. Conclusions: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low level tobacco smoke exposure to lung health risk, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke. Affymetrix arrays were used to assess the gene expression data of smoking-responsive genes in the in small airway epithelium obtained by fiberoptic bronchoscopy of 48 healthy non-smokers (non-smoker or Nsaets), 65 healthy smokers (smoker), 7 symptomatic smokers (SYMs) and a healthy occasional smoker (OcSs). YSB and LO contributed equally to the study.
2011-02-02 | E-GEOD-19667 | biostudies-arrayexpress