E-MTAB-6909
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-6909 | ExpressionAtlas | 2018-09-17
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:The first step in the development of human colorectal cancer (CRC) is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (APC) gene which encodes an essential tumor suppressor. In order to identify genes affected by Apc loss, expression profiling of intestinal epithelium isolated from mice harboring the conditional allele of the gene was performed. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation. To characterize the gene signature in colon upon Msx1 depletion, colonic epithelium from mice harboring conditional alleles of Apc and Msx1 was isolated and the gene expression profile was compared with control mice harboring the conditional allele of Apc only.
2019-11-01 | E-MTAB-6909 | biostudies-arrayexpress
Project description:The first step in the development of human colorectal cancer (CRC) is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (APC) gene encoding an essential tumor suppressor. In order to identify genes affected by Apc loss, expression profiling of intestinal epithelium isolated from mice harboring the conditional allele of the gene was performed. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation. Subsequently, the expression pattern of human MSX1 was examined in a collection of colonic tumors. The MSX1 mRNA level was increased in all types of human intestinal neoplasia tested. In order to identify genes affected by MSX1 loss, expression profiling of human colorectal cancer cells SW620 upon MSX1 gene depletion was performed.
2019-11-01 | E-MTAB-6928 | biostudies-arrayexpress
Project description:The first step in the development of human colorectal cancer is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (Apc) gene encoding an essential tumor suppressor. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation in intestinal epithelium isolated in mice harboring the conditional allele of the Apc gene. To identify the gene signature in the small intestine upon Msx1 depletion, small intestinal epithelium from mice harboring conditional alleles of Apc and Msx1 was isolated and the gene expression profile was compared with control mice harboring the conditional allele of Apc only.
2019-11-01 | E-MTAB-6930 | biostudies-arrayexpress
Project description:Brg1 has been reported to act as a trans-activator for the Wnt pathway by interacting with beta-catenin. Given this interaction and the crucial role Wnt signalling plays in the intestinal homeostasis, we aimed to investigate the effect of Brg1 loss on gene expression in normal and Wnt activated small intestinal epithelium. We used VillinCreERT2 Cre recombinase and loxP targeted allels of Brg1 and Apc to generate 4 cohorts of conditional knock-out mice: Cre-negative controls (n=4), Brg1 deficient (n=4), Apc deficient (n=3) and double Brg1-Apc deficient (n=4). All mice were induced by 4x80mg/kg daily injections of Tamoxifen. Epithelium enriched (gut scrapes) samples of small intestine (jejunum) were collected at day 4 post induction. Loss of Brg1 expression in the small intestinal epithelium at this time point was confirmed by immunohistochemistry.
2013-08-07 | E-GEOD-46129 | biostudies-arrayexpress
Project description:Progression of nonmalignant colonic cells harboring somatic mutations depends upon interactions with surrounding stroma; however, details of this interaction are poorly understood. We performed targeted transcriptional profiling of laser-captured epithelial and stromal cells from ACF, the earliest detectable human colonic pre-neoplastic lesion. Within ACF epithelium carrying non-overlapping mutations in KRAS, BRAF, or APC, we observed broad NF-kB-related inflammatory changes and specific differences associated with each mutation, including BRAFV600E-mediated senescence. Additionally, we identified ACF-associated stromal changes indicative of immune cell infiltration and fibroblast activation. Our results provide new insight into intercellular signaling changes that control the earliest stages of CRC development.
2016-11-23 | GSE77312 | GEO
Project description:Transcriptional profiling of mouse intestinal crypt epithelial cells comparing Apc+/Î716 mice with Apc+/Î716 Id2-/- mice. One-condition experiment, Apc+/Î716 mice vs. Apc+/Î716 Id2-/- mice, Biological replicates: 1 pooled intestinal crypt epithelium from 3 Apc+/Î716 mice, 1 pooled intestinal crypt epithelium from 3 Apc+/Î716 Id2-/- mice. One replicate per array.
2016-03-01 | E-GEOD-66480 | biostudies-arrayexpress
Project description:Tumours depend on altered rates of protein synthesis for growth and survival, suggesting that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools and strains energy resources and causes MYC-dependent apoptosis. eIF2B5 limits MYC expression and prevents apoptosis in APC-deficient murine and patient-derived organoids and in APC-deficient murine intestinal epithelia in vivo. Conversely, the high MYC levels present in APC-deficient cells induce phosphorylation of eIF2alpha via the GCN2 and PKR kinases. Pharmacological inhibition of GCN2 phenocopies eIF2B5 depletion and has therapeutic efficacy in tumour organoids, demonstrating that a negative MYC/eIF2alpha feedback loop constitutes a targetable vulnerability of colorectal tumours.
2019-11-04 | GSE106858 | GEO
Project description:The goal of this study is to study the consequence of EEC loss on the colonic epithelium through tissue specific deletion of the transcription factor Ngn3.
2019-07-13 | GSE134202 | GEO
Project description:Loss of the APC tumor suppressor in the intestinal epithelium initiates the majority of human colorectal adenocarcinomas. Constitutive β-catenin activation is thought to underlie tumorigenesis induced by loss of APC, however β-catenin activation alone does not recapitulate all APC-loss phenotypes, suggesting that additional pathways are required. We demonstrate that aberrant activation of the Msi1 RNA binding protein occurs upon APC loss and that constitutive Msi1 activation alone is sufficient to phenocopy APC loss in the intestinal epithelium. Msi1 elicits these effects through binding of mRNAs encoding pleiotropic tumor suppressors resulting in promiscuous activation of quiescent intestinal stem cells, proliferative expansion of the stem cell compartment, crypt fission, and blocked differentiation. Further, we find these phenotypes to be largely dependent on mTORC1 activity, and demonstrate that loss of Msi activity is sufficient to abrogate tumorigenesis in mouse and human systems. Our findings implicate Msi1 as a central coordinator of APC loss-induced intestinal stem cell transformation and adenocarcinoma progression. 2 wild-type, 2 transgenic samples
2015-10-22 | E-GEOD-54598 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide Unique combinations of mutations can affect responsiveness to specific therapeutics. This can be, at least in part, due to mutation-specific alterations in gene regulatory mechanisms. To better understand how unique combinations of mutations affect gene regulation, we generated small RNA-seq, length extension chromatin run-on-seq (leChRO-seq), and RNA-seq data from APC (A-mutant), APC/KRAS (AK-mutant), APC/KRAS/TP53 mutant (AKP-mutant), and iGFP control human colonic organoids. From these analyses, we found that our colonic organoid models demonstrate mutation-specific patterns of miRNA transcription, miRNA expression and transcriptional regulatory element actvitiy. Furthermore, we defined 10 patterns of miRNA expression across organoid models. We highlighted one group of miRNAs that exhibited a unique downregulation of expression in AKP-mutant organoids (including miR-34a-5p and miR-10a-5p). Analysis of miRNA transcription revealed that most changes in miRNA expression are correlated with changes in miRNA transcription. Analysis of leChRO-seq data revealed that transcriptional regulatory elements upregulated in AKP-mutant colonic organoids have an enrichment of predicted binding sites for oncogenic transcription factors.
2023-12-31 | GSE231436 | GEO