CDH1 knockout in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54234 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA236013
REPOSITORIES: GEO
Similar Datasets
Project description:Employing Cre/loxP technology, a mouse model of liver specific Cdh1 (E-cadherin) depletion was created (fl/fl | +/wt). Previously, the mice had already been compared to littermates with normal Ecadherin levels (fl/fl | wt/wt), using a broad range of laboratory methods (Serum parameters, long-term weight analysis, histology, western blot, etc.). To analyze the effect of Cdh1 (E-Cadherin) depletion on the liver homeostasis on the RNA-level over the course of 3 time-points, liver tissue was aquired from mice groups aged 1 week, 3 weeks and 6 weeks. Mice with liver-specific Cdh1 depletion were compared to wildtype-like littermates. 1 week: n=2+2; 3 weeks: n=3+3; 6 weeks: n=3+3. Samples (mice) were not paired.
2014-07-01 | E-GEOD-54234 | biostudies-arrayexpress
Project description:We wished to investigate the role of E-cadherin loss in our mouse parietal cell/pre-parietal cell E-cadherin knock-out, p53 knock-out, oncogenic Kras induced model of gastric cancer. As such, we isolated RNA from stomach tissue from our E-cadherin knock-out model (Atp4b-Cre;Cdh1(fl/fl);Kras(LSL-G12D/+);Trp53(fl/fl);Rosa26(LSL-YFP/LSL-YFP)) and our E-cadherin heterozygous model (Atp4b-Cre;Cdh1(fl/+);Kras(LSL-G12D/+);Trp53(fl/fl);Rosa26(LSL-YFP/LSL-YFP)). We then performed a microarray on this stomach tissue from four independent mice of each genotype. Differentially expressed genes were identified and gene set overlap analysis was used to identify pathways enriched in one model over the other.
2018-05-01 | E-MTAB-5833 | biostudies-arrayexpress
Project description:We conducted transcriptome analysis usin next generation sequencing of paired WT or CDH1 KO hGO cells established from three patients' fundic gands. Compared to WT hGOs, CDH1 KO hGO cells showed higher expression of matrix metalloproteinase (MMP) genes and genes that regulate inflammation and angiogenesis. We showed that the migration ability of CDH1 KO hGO cells was mediated by upregulation of MMPs and this effect was abolished by specific inhibitor of MMPs in vitro. MMP-3 protein was expressed in clinical samples of E-cadherin deficient signet ring cell carcinoma (SRCC) of the stomach. Our study represents that MMPs are promising candidates for novel therapeutic targets for E-cadherin-deficient SRCC.
2023-03-10 | GSE146716 | GEO
Project description:E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach. Results: In this sense we have searched for additional CDH1 transcripts arising from intron 2. From the four found, one (CDH1a) was demonstrated to be tissue specific and to be translated in vivo. When overexpressed in an E-cadherin negative context CDH1a replaced the canonic protein functions Conclusions: We have demonstrated, for the first time, transcripts arising from CDH1 intron 2. One of these, CDH1a, was found to modulate E-cadherin function representing a novel mechanism underlying invasion and angiogenesis in epithelial cancers and opening the way for novel therapeutic approaches. Total RNA obtained from human gastric tubular adenocarcinoma Mkn28 cell line. Three independent replicas of each conditions(i.e pLenti transduced cell lines overexpressing CDH1a , pLenti with empty vector and pLenti transduced cell lines overexpressing wild type CDH1) has been employed.
2012-08-01 | E-GEOD-32540 | biostudies-arrayexpress
Project description:Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT). Methods: To improve our understanding of how E-cadherin loss contributes to tumorigenicity, we investigated the impact of its elimination from the non-tumorigenic breast cell line MCF10A. We performed cell-based assays and whole genome RNAseq to characterize an isogenic MCF10A cell line that is devoid of CDH1 expression due to an engineered homozygous 4bp deletion in CDH1 exon 11. Results: The E-cadherin-deficient line, MCF10A CDH1-/- showed subtle morphological changes, weaker cell-substrate adhesion, delayed migration, but retained cell-cell contact, contact growth inhibition and anchorage-dependent growth. Within the cytoskeleton, the apical microtubule network in the CDH1-deficient cells lacked the radial pattern of organization present in the MCF10A cells and F-actin formed thicker, more numerous stress fibres in the basal part of the cell. Whole genome RNAseq identified compensatory changes in the genes involved in cell-cell adhesion while genes involved in cell-substrate adhesion, notably ITGA1, COL8A1, COL4A2 and COL12A1, were significantly downregulated. Key EMT markers including CDH2, FN1, VIM and VTN were not upregulated although increased expression of proteolytic matrix metalloprotease and kallikrein genes was observed. Conclusions: Overall, our results demonstrated that E-cadherin loss alone was insufficient to induce an EMT or enhance transforming potential in the non-tumorigenic MCF10A cells but was associated with broad transcriptional changes associated with tissue remodelling. Examination of the impact of E-cadherin (CDH1) loss in an isogenic pair of breast cell lines.
2014-08-01 | E-GEOD-59317 | biostudies-arrayexpress
Project description:To futher understand the properties of CDH1+ GSCs and CDH1- GSCs, flow cytometry was used to sort the twopopulations after trypsin digestion and they were compared by total RNA sequencing (RNA-seq). The data clearlyshowed CDH1+ and CDH1- cells as having highly distinct profiles. In particular, numerous epithelial genes (e.g.Dsp, Pkp2, Krt19) were highly expressed in the CDH1+ population. In contrast, most genes known to be generalmarkers of SSCs/undifferentiated spermatogonia were downregulated (e.g. GFRA1 and ID4) or unchanged (e.g. ZBTB16and SALL4) in CDH1- GSCs. Additionally, KEGG pathway analysis revealed that the two populations exhibiteddistinctive activity in several signaling pathways including WNT and TGFb signaling. Notably, Tgfbr1, Smad2, Smad3tended to be lower in CDH1+ GSCs while Smad7, an inhibitor of TGFb signaling, was higher.The results showed thatCDH1+ GSCs were more epithelial in nature compared to CDH1- GSCs and supported the notion that CDH1+ GSCs are areable to partly overcome MET barrier because they may be in an advanced stage of MET.
2017-03-01 | GSE90712 | GEO
Project description:E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach. Results: In this sense we have searched for additional CDH1 transcripts arising from intron 2. From the four found, one (CDH1a) was demonstrated to be tissue specific and to be translated in vivo. When overexpressed in an E-cadherin negative context CDH1a replaced the canonic protein functions Conclusions: We have demonstrated, for the first time, transcripts arising from CDH1 intron 2. One of these, CDH1a, was found to modulate E-cadherin function representing a novel mechanism underlying invasion and angiogenesis in epithelial cancers and opening the way for novel therapeutic approaches.
2012-08-02 | GSE32540 | GEO
Project description:Liver-specific depletion of HDAC3 leads to liver steatosis (fatty liver), suggesting disregulation of lipid metabolism. This is correlated with changes in lipid metabolic gene expression. Livers depleted of HDAC3 were removed from 12 week old male HDAC3 fl/fl mice (loxP sites flanking exon 4 to 7 of the HDAC3 gene encoding the catalytic domain of HDAC3) one week after the injection of AAV2/8-Tbg-Cre virus. Livers from the HDAC3 fl/fl mice injected with AAV2/8-Tbg-GFP were used as normal controls.
2011-03-11 | GSE25937 | GEO
Project description:BACKGROUND & AIMS: Gastric cancer is the second most frequent cause of death from cancer in the world, diffuse-type gastric cancer (DGC) exhibiting a poor prognosis. Germline mutations of CDH1, encoding E-cadherin, have been reported in hereditary DGCs, and genetic and/or epigenetic alterations of CDH1 are frequently detected in sporadic DGCs. Genetic alterations of TP53 are also frequently found in DGCs. To examine the synergistic effect of loss of E-cadherin and p53 on gastric carcinogenesis, we established a mouse line in which E-cadherin and p53 are specifically inactivated in the stomach parietal cell lineage. METHODS: We crossed Atp4b-Cre mice with Cdh1loxP/loxP and Trp53loxP/loxP mice, and examined the gastric phenotype of Atp4b-Cre+;Cdh1loxP/loxP;Trp53loxP/loxP mice. RESULTS: Non-polarization of E-cadherin-negative parietal cells and proton pump-negative atypical foci were observed in the transgenic mice. Intramucosal cancers and invasive cancers composed of poorly differentiated carcinoma cells and signet ring cells, which were histologically very similar to those in humans, were found from 6 and 9 months, respectively. Fatal DGCs developed at 100% penetrance within a year, frequently metastasized to lymph nodes, and had tumorigenic activity in immunodeficient mice. Gene expression profiling analyses also revealed that DGCs in the E-cadherin/p53-deficient mice resembled human DGCs. CONCLUSIONS: Our mouse line is the first genetically modified mouse model of DGC and very useful for clarifying the mechanism underlying gastric carcinogenesis, and provides a new approach to the treatment and prevention of DGC because of morphological and biochemical similarities with human DGC.
2011-12-04 | GSE25302 | GEO
Project description:BACKGROUND & AIMS: Gastric cancer is the second most frequent cause of death from cancer in the world, diffuse-type gastric cancer (DGC) exhibiting a poor prognosis. Germline mutations of CDH1, encoding E-cadherin, have been reported in hereditary DGCs, and genetic and/or epigenetic alterations of CDH1 are frequently detected in sporadic DGCs. Genetic alterations of TP53 are also frequently found in DGCs. To examine the synergistic effect of loss of E-cadherin and p53 on gastric carcinogenesis, we established a mouse line in which E-cadherin and p53 are specifically inactivated in the stomach parietal cell lineage. METHODS: We crossed Atp4b-Cre mice with Cdh1loxP/loxP and Trp53loxP/loxP mice, and examined the gastric phenotype of Atp4b-Cre+;Cdh1loxP/loxP;Trp53loxP/loxP mice. RESULTS: Non-polarization of E-cadherin-negative parietal cells and proton pump-negative atypical foci were observed in the transgenic mice. Intramucosal cancers and invasive cancers composed of poorly differentiated carcinoma cells and signet ring cells, which were histologically very similar to those in humans, were found from 6 and 9 months, respectively. Fatal DGCs developed at 100% penetrance within a year, frequently metastasized to lymph nodes, and had tumorigenic activity in immunodeficient mice. Gene expression profiling analyses also revealed that DGCs in the E-cadherin/p53-deficient mice resembled human DGCs. CONCLUSIONS: Our mouse line is the first genetically modified mouse model of DGC and very useful for clarifying the mechanism underlying gastric carcinogenesis, and provides a new approach to the treatment and prevention of DGC because of morphological and biochemical similarities with human DGC. Two-condition experiment, Gastric cancer vs. normal gastric mucosal tissues. Biological replicates: pooled control sample from five normal gastric mucosal tissues, three replicates from diffuse-type gastric cancer.
2011-12-04 | E-GEOD-25302 | biostudies-arrayexpress