Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA203398 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis. RNA was isolated from newborn mouse epidermis.Gene expression profiling was on on Affymetrix 430-2.0 platform.
2013-05-18 | E-GEOD-47065 | biostudies-arrayexpress
Project description:Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis.
2013-05-18 | GSE47065 | GEO
Project description:Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146 and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 demonstrated single agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both Cisplatin and IR in vitro. The triple combination R1507-Cisplatin-IR led to a dramatic delay in tumor growth compared to Cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis and survival. Finally, we identified that the nucleotide excision repair pathway (NER) was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard Cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting. We used microarrays to investigate the effect of IGF-1R targetting on the global gene expression. Gene expression data from H526 xenografts under various treatment and time conditions Total mRNA from 33 NCI-H526 SCLC (small-cell lung cancer) xenografts was hybridized to Affymetrix HGU133 Plus 2.0 expression arrays. Log2 gene expression values were calculated using RMA. (A) To identify the molecular mechanisms involved in the response to R1507 alone along the treatment time, we performed global gene expression profiling in H526 xenografts at the following time points: baseline (vehicle), R1507 day 1 and R1507 day 7. (B) To identify the molecular mechanisms involved in the response to CDDP- and IR-R1507 combinations, we performed global gene expression profiling on mice bearing H526 xenografts treated with the following treatment conditions: vehicle, R1507 CDDP, IR, CDDP-R1507 and IR-R1507.
2013-03-30 | E-GEOD-45626 | biostudies-arrayexpress
Project description:Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146 and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 demonstrated single agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both Cisplatin and IR in vitro. The triple combination R1507-Cisplatin-IR led to a dramatic delay in tumor growth compared to Cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis and survival. Finally, we identified that the nucleotide excision repair pathway (NER) was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard Cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting. We used microarrays to investigate the effect of IGF-1R targetting on the global gene expression.
2013-03-30 | GSE45626 | GEO
Project description:Although Insulin-like Growth Factor (IGF-1) signaling promotes tumor growth and cancer progression, IGF-1 Receptor-targeted therapies have shown poor clinical efficacy. The mechanistic basis for this is unclear as is our understanding of what distinguishes IGF-1R signaling from the closely related Insulin receptor (IR) signaling. This study illuminates both issues. A site in the IGF-1R C-terminal tail incorporating two tyrosines that are not present in the Insulin receptor (IR) was previously shown to be essential for IGF-1-mediated cancer cell survival, migration and tumorigenic growth. Here, we establish that the Y1250/Y1251 site is autophosphorylated in a cell adhesion-dependent manner.
2020-05-15 | PXD017644 | Pride
Project description:Mammary Tissue: Wild type mammary glands vs IGF-IR induced mammary tumors vs IGF-IR independent tumors
| PRJNA147647 | ENA
Project description:Despite a high degree of homology, insulin and IGF-1 receptors (IR/IGF1R) mediate distinct cellular and physiological functions. Here, using chimeric and site-mutated receptors, we demonstrate how domain differences between IR and IGF1R contribute the distinct functions of these receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to its higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. We generated mouse brown preadipocytes in which both insulin and IGF-1 receptors (IR and IGF1R) had been genetically inactivated using Cre-lox recombination. These IR and IGF1R DKO cells were then reconstituted with wild-type mouse IR, IGF1R, or one of two chimeric receptors: IR/IGF1R with the IR extracellular domain (ECD) fused to the IGF1R transmembrane and intracellular domains (ICD) and IGF1R/IR with the ECD of IGF1R fused to the ICD domains of IR. Three independent clones for each line were used for the study. For expression analysis, we serum-starved the preadipocytes clones overnight and stimulated cells with 100 nM insulin, IGF-1 or vehicle for 6 h, and subjected the cellular RNA to analysis using Affymetrix Mouse Gene 2.0 ST arrays.
2016-07-01 | E-GEOD-81921 | biostudies-arrayexpress
Project description:The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in developmental and cancer biology. Most of its biological effects have been ascribed to its tyrosine kinase activity. We report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear IGF-1R associated with enhancer-like elements and increased transcription in reporter assays. We used ChIP-seq to examine the interaction of IGF-1R with DNA on a genome-wide scale. Analysis of the data set resulted in 568 candidate peaks, that is, statistically significant IGF-1R-enriched regions. The IGF-1R-enriched regions were divided into five classes on the basis of their location relative to known genes. Most of the IGF-1R-interacting sites (80%) were located distal from any annotated gene (intergenic), 6.3% were located in introns, 6.3% in exons, 3.4% were <20 kb upstream of an annotated transcript start site (5'UTR + 20 kb upstream), and 3.6% were <20 kb downstream of an annotated transcript end site (3'UTR + 20 kb downstream).
2010-08-25 | GSE23792 | GEO
Project description:The important role of IGF-1R in cancers has been well established. Classical model involves IGF-1/2 binding to IGF-1R, following activation of the PI3K/Akt pathway, thereby promoting cell proliferation, apoptosis inhibition and treatment resistance. While IGF-1R has become a promising target for cancer therapy, clinical disclosures subsequently have been less encouraging. The question is whether targeting IGF/IGF-1R still holds therapeutic potential. Here we show a novel mechanism that knockdown IGF-1R surprisingly triggers cytoplasmic viral RNA sensors MDA5 and RIG-1, leading to mitochondrial apoptosis in cancer. We analyzed MDA5 and RIG-1 in the intestinal epithelium of IGF-1R knockdown mice. Igf1r+/- mice demonstrated higher MDA5 and RIG-1 than WT mice. IGF-1R knockdown-triggered MDA5 and RIG-1 was further analyzed in human cancer and normal cells. Increased MDA5 and RIG-1 were clearly seen in the cytoplasm identified by immunofluoresce in the cells silenced IGF-1R. Block off IGF-1R downstream PI3K/Akt did not impact on MDA5 and RIG-1 expression. IGF-1R knockdown-triggered MDA5 and RIG-1 and their signaling pathways were similar to those of viral RNA mimetic poly(I:C) had. IGF-1R knockdown-triggered MDA5 and RIG-1 led to cancer apoptosis through activation of the mitochondrial pathway. In vivo assay, Igf1r+/- mice strongly resisted AOM-induced colonic tumorigenesis through triggering MDA¬5- and RIG-1-mediated apoptosis. Notably, RIG-I and MDA5-mediated proapoptotic signaling pathway is preferential active in cancer cells. These data suggest that targeting IGF-1R-triggered MDA5 and RIG-1 might have therapeutic potential for cancer treatment.
2019-11-30 | GSE122534 | GEO
Project description:The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in developmental and cancer biology. Most of its biological effects have been ascribed to its tyrosine kinase activity. We report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear IGF-1R associated with enhancer-like elements and increased transcription in reporter assays. We used ChIP-seq to examine the interaction of IGF-1R with DNA on a genome-wide scale. Analysis of the data set resulted in 568 candidate peaks, that is, statistically significant IGF-1R-enriched regions. The IGF-1R-enriched regions were divided into five classes on the basis of their location relative to known genes. Most of the IGF-1R-interacting sites (80%) were located distal from any annotated gene (intergenic), 6.3% were located in introns, 6.3% in exons, 3.4% were <20 kb upstream of an annotated transcript start site (5'UTR + 20 kb upstream), and 3.6% were <20 kb downstream of an annotated transcript end site (3'UTR + 20 kb downstream). Analysis of the genomic interaction of IGF1R in DFB cells
2010-08-25 | E-GEOD-23792 | biostudies-arrayexpress