Human melanoma cells over-express Extracellular Matrix 1 (ECM1) which is regulated in part by TFAP2C
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41234 | GEO | 2012/10/02
SECONDARY ACCESSION(S): PRJNA176308
REPOSITORIES: GEO
Similar Datasets
Project description:Extracellular Matrix 1(ECM1) expression is increased in multiple tumor cell lines and primary cancers. Activator protein 2C (TFAP2C) is a potent regulator of ECM1 transcription. TFAP2C may contribute to the increased ECM1 expression noted in many cancers. This is the first report identifying the minimal promoter region of the human ECM1 gene and its regulation by TFAP2C Human A375 melanoma cells were assessed for mRNA and protein expression of ECM1. A mininal promoter region for ECM1 transactivation was identified. ECM1 expression was regulated in part by TFAP2C, and in ChIP-Seq experiments, TFAP2C was found to bind directly to the ECM1 gene in A375 melanoma cells and in MCF7 breast cancer cells.
2012-10-02 | E-GEOD-41234 | biostudies-arrayexpress
Project description:Extracellular matrix 1 (ECM1) is over-expressed in multiple epithelial malignancies. However, knowledge regarding the expression of ECM1 in melanomas and the mechanisms of ECM1 regulation is limited. In this study, we found that ECM1 is over-expressed in several melanoma cell lines, when compared to primary melanocytes, and furthermore, that ECM1 expression paralleled that of TFAP2C levels in multiple cell lines. Knockdown of TFAP2C in the A375 cell line with siRNA led to a reduction in ECM1 expression, and upregulation of TFAP2C with adenoviral vectors in the WM793 cell line resulted in ECM1 upregulation. Utilizing 5' RACE to identify transcription start sites (TSS) and luciferase reporter assays in the ECM1-overexpressing A375 cell line, we identified the minimal promoter region of human ECM1 and demonstrate that an approximately 100bp fragment upstream of the TSS containing a TATA box and binding sites for AP1, SP1 and Ets is sufficient for promoter activity. Chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in the A375 cell line identified an AP2 regulatory region in the promoter of the ECM1 gene. Gelshift assays further confirmed binding of TFAP2C to this site. ECM1 knockdown reduces melanoma cell attachment and is consistent with findings that ECM1 overexpression has been associated with a poor prognosis. Our investigations show an as yet unrecognized role for TFAP2C in melanoma via its regulation of ECM1.
| S-EPMC3759440 | biostudies-literature
Project description:Molecular subtypes of breast cancer are characterized by patterns of gene expression, which can be used to predict response to therapy and overall clinical outcome. The luminal breast cancer subtypes are defined by the expression of ER-alpha (ERa) and a set of ERa-associated genes. The transcription factor activator protein 2C (TFAP2C, AP-2C, AP-2g) transcription factor plays a critical role in regulating cell growth and differentiation during ectodermal development and has been implicated in the regulation of ERa and other luminal-associated genes in breast cancer. While TFAP2C has been established as a prognostic factor in human breast cancer, the role of TFAP2C in development of the luminal epithelial cells in the normal mammary gland and in breast cancer have remained elusive. Herein, we demonstrate a critical role of TFAP2C in maintaining the luminal differentiation phenotype during normal mammary development and in luminal breast carcinoma cell lines. Total RNA from MCF7 cells with and without knockdown of TFAP2c. 3 biological replicates, with 2 technical replicates each, were performed for each sample type.
2014-02-01 | E-GEOD-44203 | biostudies-arrayexpress
Project description:Molecular subtypes of breast cancer are characterized by patterns of gene expression, which can be used to predict response to therapy and overall clinical outcome. The luminal breast cancer subtypes are defined by the expression of ER-alpha (ERa) and a set of ERa-associated genes. The transcription factor activator protein 2C (TFAP2C, AP-2C, AP-2g) transcription factor plays a critical role in regulating cell growth and differentiation during ectodermal development and has been implicated in the regulation of ERa and other luminal-associated genes in breast cancer. While TFAP2C has been established as a prognostic factor in human breast cancer, the role of TFAP2C in development of the luminal epithelial cells in the normal mammary gland and in breast cancer have remained elusive. Herein, we demonstrate a critical role of TFAP2C in maintaining the luminal differentiation phenotype during normal mammary development and in luminal breast carcinoma cell lines.
2014-02-01 | GSE44203 | GEO
Project description:We report the differential gene expression between ECM1- sufficient and -deficient peritoneal macrophage. Inflammatory bowel disease (IBD) comprises chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Here, we uncover a new function of extracellular matrix protein 1 (ECM1) in promoting the pathogenesis of human and mouse IBD. ECM1 was highly expressed in macrophages, particularly tissue-infiltrated macrophages under inflammatory conditions, and ECM1 expression was significantly induced during IBD progression. The macrophage-specific knockout of ECM1 resulted in increased arginase 1 (ARG1) expression and impaired polarization into the M1 macrophage phenotype following LPS treatment.RNA-sequencing data indicated an alternative metabolic process and a higher arginine metabolic level in ECM1-deficient macrophages compared with ECM1-sufficient macrophages. A mechanistic study showed that ECM1 can negatively regulate M1 macrophage polarization through the GM-CSF/STAT5 signalling pathway. Pathological changes in mice with dextran sodium sulphate-induced IBD were alleviated by the specific knockout of the ECM1 gene in macrophages. Taken together, our findings show that ECM1 has an important function in promoting M1 macrophage polarization, which is critical for controlling inflammation and tissue repair in the intestine.
2019-11-22 | GSE140766 | GEO
Project description:CD4+ helper T cells are critical for immunological response. Th2 cells, a subset of CD4+ helper T cells, are responsible for asthma and other immune diseases. We found a Th2 secreted protein, ExtraCellular Matrix protein 1 (ECM1), which is highly induced by classic IL-4 signaling pathway during helper T cells differentiation. We used microarrays to clarify the global programme of gene expression difference underlying fully developed Th2 cells from WT and ECM1 KO mice and identified distinct classes of up and down regulated genes by ECM1.
2010-12-31 | GSE19707 | GEO
Project description:CD4+ helper T cells are critical for immunological response. Th2 cells, a subset of CD4+ helper T cells, are responsible for asthma and other immune diseases. We found a Th2 secreted protein, ExtraCellular Matrix protein 1 (ECM1), which is highly induced by classic IL-4 signaling pathway during helper T cells differentiation. We used microarrays to clarify the global programme of gene expression difference underlying fully developed Th2 cells from WT and ECM1 KO mice and identified distinct classes of up and down regulated genes by ECM1. Naïve CD4+ T cells are seperated from WT and ECM1 mice, cultured and harveseted for RNA extraction and hybridization on Affymetrix microarrays.
2010-12-31 | E-GEOD-19707 | biostudies-arrayexpress
Project description:Extracellular Matrix Protein-1 (ECM1) promotes tumorigenesis in multiple organs, but the mechanisms associated with the functions and putative receptors of ECM1 subtypes have yet to be systematically clarified. We found in this study that secretory ECM1a functions as an oncoprotein to induce tumorigenesis through binding of the Gly-Pro-Arg (GPR) motif to integrin aXb2 and activation of AKT/FAK/Rho/cytoskeletal signaling. Nonsecretory ECM1b binds to myosin to block myosin phosphorylation, thus preventing cytoskeletal signaling activation and tumorigenesis. Based on RNA sequencing, we further found that the heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) protein induced by ECM1a favors the alternative mRNA splicing of ECM1a to control ECM1-associated signaling and tumorigenesis. ATP binding cassette subfamily G member 1 (ABCG1) transduces ECM1a-integrin aXb2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cisplatin resistance in cancer cells through upregulation of CD326-mediated cell stemness.
2021-05-27 | GSE171425 | GEO
Project description:Our work has shown that the transcription factor TFAP2C is upregulated in fibroblasts that generate an anisotrophic extracellular matrix. To determine what is acting downstream of TFAP2C we compared fibroblasts that had been mock transfected, or treated with a non-targeting siRNA control or siRNA against TFAP2C.
2019-10-31 | GSE121536 | GEO
Project description:The complexity of gene regulation has created obstacles to defining mechanisms that establish the patterns of gene expression characteristic of the different clinical phenotypes of breast cancer. Transcription factor TFAP2C plays a critical role in the regulation of both estrogen receptor-alpha (ERM-NM-1) and c-ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines representing different clinical phenotypes. Comparing the genomic binding sites for TFAP2C in the various cell lines, we identified that glutathione peroxidase (GPX1) is regulated by TFAP2C through an AP-2 regulatory region in the promoter of the GPX1 gene. Knock-down of TFAP2C, but not the related factor TFAP2A, resulted in an abrogation of GPX1 expression. Selenium-dependent GPX activity correlated with endogenous GPX1 expression, and overexpression of exogenous GPX1 induced GPX activity and significantly increased resistance to tert-butyl hydroperoxide. Methylation of the CpG island encompassing the AP-2 regulatory region was identified in cell lines where TFAP2C failed to bind the GPX1 promoter and GPX1 expression was unresponsive to TFAP2C. Furthermore, in cell lines where GPX1 promoter methylation was associated with gene silencing, treatment with 5-aza-dC (an inhibitor of DNA methylation) resulted in activation of GPX1 RNA and protein expression. Methylation of the GPX1 promoter was identified in approximately 20% of primary breast cancers and a highly significant correlation between TFAP2C and GPX1 expression was confirmed when considering only those tumors with an unmethylated promoter, whereas the related factor, TFAP2A, failed to demonstrate a correlation. The results demonstrate that TFAP2C regulates the expression of GPX1, which influences the redox state and sensitivity to oxidative stress induced by peroxides. Given the established role of GPX1 in breast cancer, the results provide an important mechanism for TFAP2C to further influence oncogenesis and progression of breast carcinoma cells. 4 ChIP-Seq data for TFAP2C in human breast carcinoma cell lines MCF-7, BT-474, MDA-MB-453 and SKBR-3.
2012-09-12 | E-GEOD-36351 | biostudies-arrayexpress