Gene expression signatures of MDCK-pTR GFP-RasV12 mCherry-β-catenin Δ131 cells cultured alone or mixed with MDCK mCherry-β-catenin Δ131 cells
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ABSTRACT:
PROVIDER: PRJNA900627 | ENA |
REPOSITORIES: ENA
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Project description:Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into apical lumen via cell competition. However, it remains elusive which internal or external factors compromise cell competition and provoke oncogenesis. Here, we examine the effect of sequential accumulation of gene mutations mimicking multi-sequential carcinogenesis on RasV12-induced cell competition. Consequently, we find that directionality of cell extrusion of RasV12 cells mosaically produced within Wnt-activated epithelia is reversed, and transformed cells are delaminated into basal lamina via non-cell autonomous MMP21 upregulation. Elevated production of MMP21 is elicited partly through NF-κB signaling, which blockage restores apical elimination of RasV12 cells. Collectively, this study demonstrates that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells and are endowed with an invasion advantage. We performed microarray analysis to search for molecules whose expression is changed in β-catenin Δ131/RasV12 cells surrounded by β-catenin Δ131 cells.
2022-11-16 | GSE217830 | GEO
Project description:Gene expression signatures of MDCK-pTR GFP-RasV12 cells cultured alone or mixed with MDCK cells
| PRJNA991983 | ENA
Project description:To investigate whether and how the presence of RasV12-transformed cells influences the gene expression profile of the neighbouring normal epithelial cells, we performed microarray analysis. Normal Madin-Darby canine kidney (MDCK) cells were co-cultured with MDCK cells expressing GFP or GFP-RasV12. GFP-negative normal MDCK cells were then collected by FACS, and expression of various genes was compared between the two conditions.
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Project description:To validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with beta-catenin siRNA and identified beta-catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published beta-catenin target genes found in the PubMed and the GEO databases. Based on the large number of beta-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study beta-catenin regulated genes and signaling pathways 12 arrays (2 cell lines, 2 treatments, 3 biological replicates)
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Project description:In nucleated cells, β-catenin, the key downstream effector of this pathway, is a dual function protein, regulating the coordination of gene transcription and cell–cell adhesion. The specific role of β-catenin in the anucleate platelet however remains elusive. Here, we performed a label-free quantitative proteomic analysis of β-catenin immunoprecipitates from human platelets identifying 9 co-immunoprecipitating proteins. GO biological pathway analysis revealed a significant enrichment of specific functional terms including 'cell adhesion', 'cell junction organization' and ‘adherens junction organization'. Our bioinformatics data suggests that human platelet β-catenin may be involved in facilitating cell adhesion and cell junctions. We found three proteins co-immunoprecipitating with β-catenin under both resting and activated conditions, four proteins under resting condition only and two proteins under activated condition only.
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Project description:Medulloblastoma is the most frequent malignant pediatric brain tumor. Considerable efforts are dedicated to identify markers that help to refine treatment strategies. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favorable patient outcome. We report a series of 72 pediatric medulloblastomas evaluated for beta-catenin immunostaining, CTNNB1 mutations, and studied by comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumor cells) in 6 cases and focal nuclear staining (<10% of cells) in 3 cases. The other cases exhibited either a signal strictly limited to the cytoplasm (58 cases) or were negative (5 cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented a strong activation of the Wnt/beta-catenin pathway. Remarkably, 5 out of these 6 tumors showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumors with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2) from diagnosis. All three patients with a focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumors represent a distinct molecular subgroup of medulloblastomas with favorable outcome, indicating that therapy de-escalation should be considered. Yet, international consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved. A series of 72 pediatric medulloblastoma tumors has been studied at the genomic level (array-CGH), screened for CTNNB1 mutations and beta-catenin expression (immunohistochemistry). A subset of 40 tumor samples has been analyzed at the RNA expression level (Affymetrix HG U133 Plus 2.0). Correlations between the genomic data, the expression data, the mutational screening, the pathological classification and clinical data is presented in the study. note: aCGH data not submitted to GEO
2009-02-02 | E-GEOD-12992 | biostudies-arrayexpress
Project description:To validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with β-catenin siRNA and identified β-catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published β-catenin target genes found in the PubMed and the GEO databases. Based on the large number of β-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study β-catenin regulated genes and signaling pathways
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Project description:Beta-catenin dependent gene expression
| PRJNA489972 | ENA