RNA sequencing of SPC-IGF1R mice
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PROVIDER: PRJEB24575 | ENA |
REPOSITORIES: ENA
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Project description:Bianconi2012 - EGFR and IGF1R pathway in lung cancer
EGFR and IGF1R pathways play a key role in various human cancers and are crucial for tumour transformation and survival of malignant cells. High EGFR and IGF1R expression and activity has been associated with multiple aspects of cancer progression including tumourigenesis, metastasis, resistance to chemotherapeutics and other molecularly targeted drugs. Here, the biological relationship between the proteins involved in EGFR and IGF1R pathways and the downstream MAPK and PIK3 networks has been modelled to study the time behaviour of the overall system, and the functional interdependencies among the receptors, the proteins and kinases involved.
This model is described in the article:
Computational model of EGFR and IGF1R pathways in lung cancer: a Systems Biology approach for Translational Oncology.
Bianconi F, Baldelli E, Ludovini V, Crinò L, Flacco A, Valigi P.
Biotechnol Adv. 2012 Jan-Feb;30(1):142-53.
Abstract:
In this paper we propose a Systems Biology approach to understand the molecular biology of the Epidermal Growth Factor Receptor (EGFR, also known as ErbB1/HER1) and type 1 Insulin-like Growth Factor (IGF1R) pathways in non-small cell lung cancer (NSCLC). This approach, combined with Translational Oncology methodologies, is used to address the experimental evidence of a close relationship among EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by in situ hybridization (FISH) and the corresponding ability to develop a more aggressive behavior. We develop a detailed in silico model, based on ordinary differential equations, of the pathways and study the dynamic implications of receptor alterations on the time behavior of the MAPK cascade down to ERK, which in turn governs proliferation and cell migration. In addition, an extensive sensitivity analysis of the proposed model is carried out and a simplified model is proposed which allows us to infer a similar relationship among EGFR and IGF1R activities and disease outcome.
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2024-09-02 | BIOMD0000000427 | BioModels
Project description:IGF1 and IGF1 receptors (IGF1R) are present in the adult heart and have been shown to be essential for myocardial performance. Insulin-like growth factor 1 (IGF1) is produced in numerous tissues particularly by the liver in response to growth hormone stimulation and is an important factor in the regulation of post-natal growth and development. We have generated and characterized transgenic mice over-expressing the IGF1R. We crossed IGF1R transgenic mice with dominant negative (dn)PI3K (p110) and with constitutively active (ca)PI3K(p110) transgenic mice. Expression profiling was performed on the ventricles of IGF1R, IGF1R-caPI3K, IGF1R-dnPI3K, caPI3K, dnPI3K transgenic female mice at 3 months of age. Non-transgenic littermates were used as controls.
2007-09-29 | E-GEOD-1143 | biostudies-arrayexpress
Project description:IGF1R (Insulin-like Growth Factor 1 Receptor) is a ubiquitously expressed transmembrane tyrosine kinase receptor with multiple functions including inflammation. IGF activity maintains human lung homeostasis, being involved in relevant pulmonary diseases with an inflammatory component, such as lung cancer, COPD, asthma and pulmonary fibrosis. Here we examined the role of IGF1R in lung inflammation using mice with a postnatal deficiency of Igf1r and a model of bleomycin(BLM)-induced lung injury. Lung transcriptome analysis of Igf1r-deficient mice showed a general inhibition of transcription of genes related to epigenetics, inflammation/immune response and oxidative stress activity with potential pulmonary protective roles. Early upon intratracheal BLM treatment, mutant mice showed improved survival and milder pulmonary injury and inflammation. Their lungs presented down-regulation of macrophage (Marco/Adgre1), neutrophil-related (Cxcl1/Ly6g), pro-inflammatory (Tnf/Il1b/Il6), endothelial adhesion (Icam1/Pecam1) and alveolar damage (Aqp5/Sftpc) markers and up-regulation of resolution phase markers (Csf1/Il13/Cd209a). Changes in mRNA of IGF system genes were also found, in parallel to a hindered response to hypoxia (Hif1a) and increased expression of the anti-oxidative stress marker Gpx8. These findings identify Igf1r as an important player in oxidative stress and inflammation and suggest that targeting Igf1r may block the inflammatory response in lung diseases with this component.
2017-07-29 | GSE88908 | GEO
Project description:The insulin-like growth factor (IGF) axis is an important signaling pathway in the growth and survival of many cell types and has been implicated in multiple aspects of cancer progression from tumorigenesis to metastasis. The multiple roles of IGF signaling in cancer suggest that selective inhibition of the pathway might yield clinically effective therapeutics. Here we describe A-928605, a novel small molecule inhibitor of the receptor tyrosine kinase responsible for IGF signal transduction. This small molecule is able to abrogate activation of the pathway as shown by effects on the target and downstream effectors and is shown to be effective at inhibiting the proliferation of an oncogene addicted tumor model cell line (CD8-IGF1R 3T3) both in vitro and in vivo. Experiment Overall Design: CD8-IGF1R 3T3 cells and 3T3 Vector control treated for 24 h with vehicle or IGF1R inhibitor A-928605, all with 3 replicates.
2009-06-11 | E-GEOD-14024 | biostudies-arrayexpress
Project description:Acute lung injury (ALI), ARDS and COVID-19 usually involve a “cytokine storm”. IGF1R (Insulin-like growth factor receptor 1) maintains lung homeostasis and is implicated in these pulmonary inflammatory diseases. In mice, widespread IGF1R deficiency was reported to counteract respiratory inflammation and alveolar damage after bleomycin (BLM)-induced ALI. To explore the molecular mechanisms mediated by Igf1r signaling after BLM challenge, we performed RNA-sequencing in lungs of IGF1R-deficient mice after BLM or saline (SAL) instillation. Transcriptomic analysis identified differentially expressed genes between BLM-challenged and SAL-treated control lungs, detecting biological processes and signaling pathways involved in ALI pathobiology. Igf1r depletion in BLM-challenged mice reversed large part of the transcriptional changes triggered by BLM, counteracting the transcriptomic profile of the inflammatory "cytokine storm". Data mining also identified changes in the expression of gene clusters with key roles in DNA damage, metabolic reprogramming, mitochondrial homeostasis, and epigenetics. Exploration of these functional groups, together with validation studies, provide new insights into the molecular mechanisms underlying the attenuating effect of Igf1r deficiency on ALI. These findings allow a more comprehensive view of IGF1R signaling at the transcriptional level, reinforcing its important role in promoting ALI and postulating it as a global epigenetic regulator in ARDS.
2024-11-01 | GSE274184 | GEO
Project description:RNA and miRNA sequencing of an IGF1R transgenic mouse model of lung cancer
| PRJNA431556 | ENA
Project description:Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury.
2017-02-09 | GSE88836 | GEO
Project description:We report RNA sequencing data from the plantaris tendons of adult male mice in the C57Bl/6 background that either have the IGF1 receptor (IGF1R) present in their tendons (Scx:IGF1R+) or mice in which IGF1R has been deleted in tenocytes expressing scleraxis (Scx:IGF1R-). Mice were created by crossing ScxCreERT2 mice with IGF1R flox/flox mice. Mice were treated with tamoxifen for 5 days to induce recombination at the IGF1R allele, and then subjected to a synergist ablation procedure in which the Achilles tendon is removed, resulting in compensatory growth of the plantaris tendon. Mice were analyzed either 7 or 14 days after synergist ablation. Control mice that did not undergo tamoxifen treatment or synergist ablation were also studied.
2019-05-28 | GSE131798 | GEO
Project description:To investigate genes that might influence resistance to infection through IGF1R, we screened human breast cancer-derived OCUB-M cells transfected with expression vector encoding IGF1R using microarray analysis. Keywords: overexpression comparison
2009-06-30 | GSE5225 | GEO
Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.
2020-06-16 | GSE138756 | GEO