Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318367 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Temproral networks of (phospho)-proteins are constructed and analyzed to infer differential interactions under insulin and IGF1 stimulation. In total, 134 antibodies are tested in 21 breast cancer cell lines. The experiments are done in triplicate. Three serum-free-condition time points (5min, 24hr, 48hr) and six stimulation time points (5min, 10min, 30min, 6hr, 24hr, and 48hr) are obtained with either 10 nM IGF1 or 10 nM insulin stimulation.
2016-07-21 | E-GEOD-80233 | biostudies-arrayexpress
Project description:Identification of filamin-A as a target for insulin and IGF1 action. Insulin analogues have been developed to achieve further improvement in the therapy of diabetes. However, modifications introduced into the insulin molecule might enhance their affinity to the insulin-like growth factor-1 receptor (IGF1R). Most tumors, including endometrial cancers, express high levels of IGF1R. The present study was aimed at identifying the entire set of genes that are differentially activated by insulin glargine or detemir, in comparison to regular insulin and IGF1, in Type 1 and Type 2 endometrial cancer cell lines (ECC-1 and USPC-1, respectively). Global gene expression analyses demonstrated a ligand-dependent up-regulated expression of filamin-A (FLNA), a gene that encodes an actin filament cross-linking protein, in both endometrial cancer cell types. Silencing experiments linked to migration assays confirmed the role of FLNA in cell growth and motility. Our data suggest that the activation of distinct sets of genes by glargine may lead to stimulation of specific pathways or, alternatively, may provide additive effects, different from those classically induced by insulin. Given that metastasis is one of the major factors contributing to the aggressiveness of tumors, the identification of FLNA as a downstream target for insulin-like hormones may be of translational relevance in cancer research. Clinical studies in endometrial cancer may add further relevant information regarding the possible differential actions of insulin analogues with respect to native insulin.
2019-01-02 | GSE109022 | GEO
Project description:Insulin analogues are designed to improve the pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode-of-action of different insulin analogues. Insulin analogues can bind the insulin receptor (INSR) and the insulin-like growth factor-1 receptor (IGF1R) with different affinities and consequently will activate different downstream signaling pathways. Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR (IRA or IRB) or the IGF1R. We sought to study the role of the different receptors (IRA, IRB and IGF1R) in the mitogenic signaling of insulin-like molecules (including insulin, glargine, X10 (or AspB10) and IGF1).
2015-01-29 | GSE65398 | GEO
Project description:Commonalities and dissimilarities between the IGF1R and INSR pathways Insulin and insulin-like growth factor-1 (IGF1), acting respectively via the insulin (INSR) and IGF1 (IGF1R) receptors, play key developmental and metabolic roles throughout life. In addition, both signaling pathways fulfill important roles in cancer initiation and progression. The inherent complexity of the INSR/IGF1R pathways, along with the well documented cross-talk between insulin-like ligands and receptors, translated into a disappointingly slow pace in the development of INSR/IGF1R-directed therapies in oncology. The present study was aimed at identifying mechanistic differences between INSR and IGF1R using a recently developed bioinformatics tool, the Biological Network Simulator (BioNSi). This application allows to import and merge multiple pathways and interaction information from the KEGG database into a single network representation. The BioNsi network simulation tool allowed us to exploit the availability of gene expression data derived from breast cancer cell lines with specific disruptions of the INSR or IGF1R genes in order to investigate potential differences in protein expression that might be linked to biological attributes of the specific receptor networks. Modeling-generated information was corroborated by experimental and biological assays. Our simulation analysis identified a number of commonalities and, most importantly, dissimilarities between the IGF1R and INSR pathways that were experimentally validated and that might help explain the basis for the biological differences between these networks.
2020-03-18 | GSE145787 | GEO
Project description:Insulin analogues are designed to improve the pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode-of-action of different insulin analogues. Insulin analogues can bind the insulin receptor (INSR) and the insulin-like growth factor-1 receptor (IGF1R) with different affinities and consequently will activate different downstream signaling pathways. Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR (IRA or IRB) or the IGF1R. We sought to study the role of the different receptors (IRA, IRB and IGF1R) in the mitogenic signaling of insulin-like molecules (including insulin, glargine, X10 (or AspB10) and IGF1). MCF7 IRA, MCF7 IRB or MCF7 IGF1R cells (as described in Arch Toxicol. 2014 Apr;88(4):953-66. doi: 10.1007/s00204-014-1201-2. Epub 2014 Jan 25.) were cultured in RPMI supplemented with 5% (v/v) CDFBS (Hyclone) and used for experiments. Cells have been exposed for 1 or 6 hours to 10 nM of the indicated insulin-like molecule. As a control sample a vehicle stimulation was performed that contained everything except the active compound.
2015-01-29 | E-GEOD-65398 | biostudies-arrayexpress
Project description:The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan.
2017-07-07 | PXD006613 | Pride
Project description:The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.
2016-09-05 | GSE64073 | GEO
Project description:Temproral networks of (phospho)-proteins are constructed and analyzed to infer differential interactions under insulin and IGF1 stimulation.
2016-07-21 | GSE80233 | GEO
Project description:The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan.
2017-05-31 | GSE99440 | GEO