Ovcar8_desi_375_10x10um_07092024
Ontology highlight
ABSTRACT:
INSTRUMENT(S): SYNAPT G2-Si
ORGANISM(S): Ovcar8 Cell Line
SUBMITTER: 
Zhibo Yang
PROVIDER: MSV000095958 | MassIVE |
REPOSITORIES: MassIVE
Similar Datasets
Project description:Expression profiling was used to identify genes differentially expressed in MSS (microsatellite stable) and MSI (microsatellite unstable) colon cancer cell lines. Data submitted in support of manuscript entitled Villin expression is frequently lost in poorly differentiated colon cancer, Diego Arango, Sheren Al-Obaidi, David S. Williams, Jose Dopeso, Rocco Mazzolini, Georgia Corner, Do-Sun Byun, Carmel Murone, Lars Tögel, Nikolajs Zeps, Lauri A. Aaltonen, Barry Iacopetta and John M. Mariadason, American Journal of Pathology, 2012. 5 microsatellite stable (MSS) and 5 microsatellite unstable (MSI) colon cancer cell lines profiled. Each cell line grown and arrayed in duplicate, and the duplicates averaged for each cell line before calculating means for MSS and MSI lines.
2012-02-07 | E-GEOD-35566 | biostudies-arrayexpress
Project description:Colorectal cancer, one of the most frequent types of malignancy in the Western world, develops through a multi-step process. The main pathways establishing transformation of normal mucosa to invasive carcinoma include chromosomal instability (CIN), microsatellite instability (MSI) or epigenetic silencing through the CpG Island Methylator Phenotype (CIMP). These pathways have distinct clinical, pathological and genetic characteristics. In general, altered cell surface glycosylation has been linked to colorectal cancer progression, however the impact of MSI-specific pathways on the glycosylation machinery of MSI colon cancer cells has not been investigated yet. In a recent study (Patsos et al., 2009) we have shown that MSI-specific mutations induce marked alterations in cell surface glycosylation, indicating specific changes in the expression of glyco-genes. Therefore the purpose of our experiment is to define these changes by glyco-gene chip analysis. Biallelic mutational inactivation of MSI target genes is believed to drive MSI tumorigenesis. TGFBR2, ACVR2 and AIM2 are among the most frequently mutated genes in MSI colorectal adenomas and carcinomas and functional studies indicate their contribution to MSI-carcinogenesis. A first general screening approach by lectin FACS analysis indicated a correlation between functional inactivation of these genes and cell surface glycosylation of the MSI colon cell line HCT116 (Patsos et al., 2009). For detailed analysis of the altered glycosylation pattern and the underlying molecular mechanisms we have established HCT116 double stable transfectants that allow doxycycline-inducible expression of the three MSI target genes TGFBR2, ACVR2 and AIM2 in a reversible manner. Thus we can experimentally control the expression of the MSI-genes and analyze short and long-term effects on different cell functions, including glycosylation. From the application of the glyco-gene chip for analysis of the transfectants we expect to gain seminal information on the influence of MSI-target genes on glycan expression and function in MSI tumor cells. Correlating loss-of-function of MSI target genes not yet linked with glycosylation to the regulation of the glycophenotype is a novel approach to investigate the glycobiology of tumor cells. In addition it is also suitable to detect new MSI-(glyco)markers for clinical applications, including diagnostic tumor markers and specific targets for immunotherapies.
2011-09-05 | E-GEOD-31927 | biostudies-arrayexpress
Project description:Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. Here we developed novel fluorescent reporter mice that show that the stem cell determinant, Musashi (Msi) is a critical element of pancreatic cancer progression. These reporters allowed functional and image based tracking of stem cell signals within cancers in vivo, revealing that Msi expression rises as PanINs progress to adenocarcinoma, and that Msi reporter+ tumor cells are the key drivers of pancreatic cancer. To visualize and track the function of live Msi-expressing cells in vivo, we developed Msi knock-in reporters in which fluorescent signals reflected endogenous Msi expression. This dataset represents pancreatic cancer_wt and pancreatic cancer_KO cells. Three wt reps and three KO reps.
2016-06-15 | E-GEOD-73312 | biostudies-arrayexpress
Project description:Synthetic lethality is a powerful approach for targeting oncogenic drivers in cancer. Recent studies revealed that cancer cells with microsatellite instability (MSI) require Werner (WRN) helicase for survival; however, the underlying mechanism remains unclear. In this study, we found that WRN depletion strongly induced p53 and its downstream apoptotic target PUMA in MSI colorectal cancer (CRC) cells. p53 or PUMA deletion abolished apoptosis induced by WRN depletion in MSI CRC cells. Importantly, correction of MSI abrogated the activation of p53/PUMA and cell killing, while induction of MSI led to sensitivity in isogenic CRC cells. Rare p53-mutant MSI CRC cells are resistant to WRN depletion due to lack of PUMA induction, which could be restored by wildtype p53 knock-in or reconstitution. WRN depletion or treatment with the RecQ helicase inhibitor ML216 suppressed in vitro and in vivo growth of MSI CRCs in a p53/PUMA_x0002_dependent manner. ML216 treatment was efficacious in MSI CRC patient-derived xenografts (PDX). Interestingly, p53 gene remains wildtype in the majority of MSI CRCs. These results indicate a critical role of p53/PUMA-mediated apoptosis in the vulnerability of MSI CRCs to WRN loss, and support WRN as a promising therapeutic target in p53-wildtype MSI CRCs.
2022-10-26 | GSE216455 | GEO
Project description:We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7), leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation were used to confirm some microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs. In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways. Case-control study. Samples were selected according to immunological criteria: those with total loss of HLA antigens and those without alterations in the expression of HLA molecules. In addition, the microsatellite instability genotype of all the samples was also analyzed, resulting in microsatellite stability (MSS) and microsatellite instability (MSI) samples. Therefore, three groups of samples were selected: MSS/HLA+, MSS/HLA-, and MSI. The MSS/HLA+ group was used as the control.
2011-02-28 | E-GEOD-27544 | biostudies-arrayexpress
Project description:Inhibition of the nonsense mediated decay (NMD) mechanism in cells results in stabilization of transcripts carrying premature translation termination codons. A strategy referred to as gene indentification by NMD inhibition (GINI) has been proposed to identify genes carrying nonsense mutations (Noensie & Dietz, 2001). Genes containing frameshift mutations in colon cancer cell line have been identifying mutatnt genes using GINI, we have now further improved the strategy. In this approach, inhibition of NMD with emetine is complemented with inhibiting NMD by blocking the phosphorylation of the hUpf1 protein with caffeine. In addition, to enhance the GINI strategy, comparing mRNA level alterations produced by inhibiting transcription alone or inhbiiting transcription together with NMD following caffeine pretreatment were used for the efficient identification of false positives produced as a result of stress response to NMD inhibition. To demonstrate the improved efficiency of this approach, we analyzed colon cancer cell lines showing microstellite instability. Bi-allelic inactivating mutations were found in the FXR1, SEC1L1, NCOR1, BAT3, PHD14, ZNF294, C190ORF5 genes as well as genes coding for proteins with yet unknown functions. Experiment Overall Design: Using GINI2 as a method of identifying novel biallelic truncating mutations in MSI+ colon cancer cells, various treatment conditions were applied to cultured colon cancer cell lines LS180 (MSI+) and SW480 (MSI-) and gene expression profiling was measured using Affymetrix GeneChip U133 Plus 2 arrays.
2008-06-13 | E-GEOD-5486 | biostudies-arrayexpress
Project description:MSI analysis using blood-derived MSI markers
| PRJEB53321 | ENA
Project description:Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. Here we developed novel fluorescent reporter mice that show that the stem cell determinant, Musashi (Msi) is a critical element of pancreatic cancer progression. These reporters allowed functional and image based tracking of stem cell signals within cancers in vivo, revealing that Msi expression rises as PanINs progress to adenocarcinoma, and that Msi reporter+ tumor cells are the key drivers of pancreatic cancer.
2016-06-15 | GSE73312 | GEO
Project description:Samples were taken from colorectal cancers in surgically resected specimens in 84 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes between MSI and MSS cancers and, furthermore, to determine the distinct characteristics of proximal and distal MSI cancers. Experiment Overall Design: Eighty-four colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures of MSI cancers, gene expression profiles were compared between MSI and MSS cancers. Next, we examined the difference in gene expression profiles between proximal and distal MSI cancers.
2008-06-13 | E-GEOD-4554 | biostudies-arrayexpress
Project description:We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7), leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation were used to confirm some microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs. In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways.
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