Gene expression profile mediated by independent E-cadherin repressors
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris Homo sapiens
PROVIDER: GSE4151 | GEO | 2006/11/02
SECONDARY ACCESSION(S): PRJNA94997
REPOSITORIES: GEO
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Project description:Gene expression profiling of MDCK epithelial cells expressing different repressors (MDCK-Snail, MDCK-Slug and MDCK-E47 cells) versus control MDCK cells. The Oncochip microarray platform v1.1 contains 9,726 clones corresponding to 6,386 different genes, and it includes 2,489 duplicate clones. Duplicate samples from each of the MDCK transfectants (E47, SNAIL, SLUG) were labeled with dUTP-Cy5 and hybridized against the dUTP-Cy3-labeled MDCK-CMV controls. Two additional hybridizations using reciprocal fluorochrome labeling were performed (dye-swap). Thus, a total of four hybridizations were performed for each condition.
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Project description:Expression profile analysis in MDCK-E47 cells in comparisom with MDCK CMV control cells Keywords: Genetic Modification (overexpression of E-cadherin repressors)
2008-12-21 | GSE9147 | GEO
Project description:Expression profile analysis in MDCK-E47 cells in comparisom with MDCK CMV control cells Keywords: Genetic Modification (overexpression of E-cadherin repressors) The Oncochip microarray platform v1.1 contains 9,726 clones corresponding to 6,386 different genes, and it includes 2,489 duplicate clones. Duplicate samples (different extrations of RNA) were labeled with dUTP-Cy5 and hybridized against dUTP-Cy3-MDCK control cells. In addittion, one RNA extraction was labelled with dUTP-Cy3 and was hybridized againts dUTP-Cy5- CMV control cells
2010-06-24 | E-GEOD-9147 | biostudies-arrayexpress
Project description:Loss of expression of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration in the developing embryo and during tumour invasion. Transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation in most carcinomas. Recently, we have identified the class I HLH transcriptional regulator E2-2 (ITF2), in a yeast one hybrid screen designed to identify transcriptional repressors interacting with the E-pal element of the murine E-cadherin promoter. The E2-2 gene codifies two isoforms that differ in their N-terminal regions but their specific functions remain unknown. In the present work we show that both E2-2A and E2-2B induce a complete EMT, in MDCK cells, with loss of E-cadherin expression, gain of mesenchymal markers and acquisition of motile and invasive properties. Although both isoforms repress E-cadherin promoter in MDCK cells, only the E2-2B isoform does it in other epithelial cell lines. Notably, we found that E2-2B is upregulated at the mRNA level in MDCK cells after treatment with TGF-ï¢1, a key regulator of EMT. Upregulation of E2-2A/B factors was confirmed in MDCK cells overexpressing other EMT inducers, Snai1, Snai2 or E47. Interestingly, gene profiling studies indicate that bHLH E2-2 factors induce similar, yet distinct, genetic programs from those induced by bHLH E47 in MDCK cells. These results, together with the expression pattern observed in early mouse embryos, support a new role for E2-2A/B in E-cadherin regulation and EMT, and suggest an interesting interplay between bHLH factors and other E-cadherin repressors. Keywords: Genetic Modification (overexpression of E-cadherin repressors) The Oncochip microarray platform v2.0 contains 13,824 clones printed by duplicate corresponding to 9,300 different genes. Each of the MDCK transfectants (E22A, E22B) were labeled with dUTP-Cy5 and hybridized against the dUTP-Cy3-labeled MDCK-CMV controls. One additional hybridizations using reciprocal fluorochrome labeling were performed (dye-swap) in each clone. Thus, a total of two hybridizations were performed for each condition.
2010-06-24 | E-GEOD-9145 | biostudies-arrayexpress
Project description:Loss of expression of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration in the developing embryo and during tumour invasion. Transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation in most carcinomas. Recently, we have identified the class I HLH transcriptional regulator E2-2 (ITF2), in a yeast one hybrid screen designed to identify transcriptional repressors interacting with the E-pal element of the murine E-cadherin promoter. The E2-2 gene codifies two isoforms that differ in their N-terminal regions but their specific functions remain unknown. In the present work we show that both E2-2A and E2-2B induce a complete EMT, in MDCK cells, with loss of E-cadherin expression, gain of mesenchymal markers and acquisition of motile and invasive properties. Although both isoforms repress E-cadherin promoter in MDCK cells, only the E2-2B isoform does it in other epithelial cell lines. Notably, we found that E2-2B is upregulated at the mRNA level in MDCK cells after treatment with TGF-beta1, a key regulator of EMT. Upregulation of E2-2A/B factors was confirmed in MDCK cells overexpressing other EMT inducers, Snai1, Snai2 or E47. Interestingly, gene profiling studies indicate that bHLH E2-2 factors induce similar, yet distinct, genetic programs from those induced by bHLH E47 in MDCK cells. These results, together with the expression pattern observed in early mouse embryos, support a new role for E2-2A/B in E-cadherin regulation and EMT, and suggest an interesting interplay between bHLH factors and other E-cadherin repressors.
2008-12-21 | GSE9145 | GEO
Project description:Temporal expression profiling was utilized to define transcriptional regulatory pathways in vivo in a mouse muscle regeneration model. Potential downstream targets of MyoD were identified by temporal expression, promoter data base mining, and gel shift assays; Slug and calpain 6 were identified as novel MyoD targets. Slug, a member of the snail/slug family of zinc finger transcriptional repressors critical for mesoderm/ectoderm development, was further shown to be a downstream target by using promoter/reporter constructs and demonstration of defective muscle regeneration in Slug null mice.
2007-11-06 | E-GEOD-469 | biostudies-arrayexpress
Project description:Temporal expression profiling was utilized to define transcriptional regulatory pathways in vivo in a mouse muscle regeneration model. Potential downstream targets of MyoD were identified by temporal expression, promoter data base mining, and gel shift assays; Slug and calpain 6 were identified as novel MyoD targets. Slug, a member of the snail/slug family of zinc finger transcriptional repressors critical for mesoderm/ectoderm development, was further shown to be a downstream target by using promoter/reporter constructs and demonstration of defective muscle regeneration in Slug null mice. Keywords: other
2003-07-16 | GSE469 | GEO
Project description:Cell plasticity is emerging as a key regulator of tumor progression and metastasis. During carcinoma dissemination epithelial cells undergo epithelial to mesenchymal transition (EMT) processes characterized by the acquisition of migratory/invasive properties, while the reverse, mesenchymal to epithelial transition (MET) process, is also essential for metastasis outgrowth. Different transcription factors, called EMT-TFs, including Snail, bHLH and Zeb families are drivers of the EMT branch of epithelial plasticity, and can be post-transcriptionally downregulated by several miRNAs, as the miR-200 family. The specific or redundant role of different EMT-TFs and their functional interrelations are not fully understood. To study the interplay between different EMT-TFs, comprehensive gain and loss-of-function studies of Snail1, Snail2 and/or Zeb1 factors were performed in the prototypical MDCK cell model system. We here describe that Snail1 and Zeb1 are mutually required for EMT induction while continuous Snail1 and Snail2 expression, but not Zeb1, is needed for maintenance of the mesenchymal phenotype in MDCK cells. In this model system, EMT is coordinated by Snail1 and Zeb1 through transcriptional and epigenetic downregulation of the miR-200 family. Interestingly, Snail1 is involved in epigenetic CpG DNA methylation of the miR-200 loci, essential to maintain the mesenchymal phenotype. The present results thus define a novel functional interplay between Snail and Zeb EMT-TFs in miR200f regulation providing a molecular link to their previous involvement in the generation of EMT process in vivo. Expression analysis of MDCK over-expression EMT-TF Analysis of 7 overexpression MDCK cells each of them using biological rpelicates (MDCK-E47, Snail2, Snail1, Twist1, Tiwst2, Zeb1, Zeb2)
2014-09-09 | E-GEOD-61217 | biostudies-arrayexpress
Project description:Cancer stem cells (CSCs) are proposed to be responsible for metastatic dissemination and clinical relapse in a variety of cancers. Analogies between CSCs and normal tissue stem cells (SC) has led to the notion that CSCs often co-opt the normal SC program of their tissue-of-origin. The cell-biological program termed epithelial-mesenchymal transition (EMT) has been found to encourage entrance of normal and neoplastic mammary cells into the corresponding SC states. Using genetically engineered knock-in reporter mouse lines, we demonstrate that in the murine mammary lineage, the paralogous EMT-inducing transcription factors Snail and Slug, are selectively exploited by CSCs and normal SCs respectively. Slug, when expressed at physiological levels, only activates a partial EMT program and is dispensable in CSCs. In contrast, Snail drives a far more complete transition into the mesenchymal state and controls both tumor-initiation and metastatic dissemination. Consistent with their functional distinctions, Snail controls far more target genes than Slug, and their distinct functions are determined by their divergent N-terminal domains. Our findings underscore fundamental distinctions between the SC program operating in normal and neoplastic SCs, and hint for potential avenues of selective therapeutic elimination of breast CSCs. We sought to understand differential ability to activate the EMT program in breast cancer cells by transcription factors Snail and Slug. Hence, we mapped genome-wide Snail and Slug binding sites in murine MMTV-PyMT breast cancer cell lines that express high level of Snail or high level of Slug respectively. Specifically, we performed Snail ChIP seq in the mesenchymal pBl.3G cells, and Slug ChIP-seq in the epithelial pBl.1G cells.
2015-09-02 | E-GEOD-61198 | biostudies-arrayexpress
Project description:The loss of E-cadherin causes dysfunction of the cell-cell junction machinery, which is an initial step in epithelial-to-mesenchymal transition (EMT), facilitating cancer cell invasion and the formation of metastases. A set of transcriptional repressors of E-cadherin (CDH1) gene expression, including Snail1, Snail2 and Zeb2 mediate E-cadherin down-regulation in breast cancer. However, the molecular mechanisms underlying the control of E-cadherin expression in breast cancer progression remain largely unknown. Here, by using global gene expression approaches, we uncover a novel function for Cdc42 GTPase-activating protein (CdGAP) in the regulation of expression of genes involved in EMT. We found that CdGAP used its proline-rich domain to form a functional complex with Zeb2 to mediate the repression of E-cadherin expression in ErbB2-transformed breast cancer cells. Conversely, knockdown of CdGAP expression led to a decrease of the transcriptional repressors Snail1 and Zeb2, and this correlated with an increase in E-cadherin levels, restoration of cell-cell junctions, and epithelial-like morphological changes. In vivo, loss of CdGAP in ErbB2-transformed breast cancer cells impaired tumor growth and suppressed metastasis to lungs. Finally, CdGAP was highly expressed in basal-type breast cancer cells, and its strong expression correlated with poor prognosis in breast cancer patients. Together, these data support a previously unknown nuclear function for CdGAP where it cooperates in a GAP-independent manner with transcriptional repressors to function as a critical modulator of breast cancer through repression of E-cadherin transcription. Targeting Zeb2-CdGAP interactions may represent novel therapeutic opportunities for breast cancer treatment.
2017-08-22 | GSE86301 | GEO