Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA156533 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. Our goal was to use integrated genomic approaches in a model of human breast cancer progression to identify core TGF-beta-regulated genes that specifically reflect the tumor suppressor activity of TGF-beta. The model consisted of the non-tumorigenic MCF10A (“M1”), the premalignant MCF10AT1k.cl2 (“M2”), the early malignant MCF10Ca1h (“M3”) and the highly malignant, metastatic MCF10Ca1a.cl1 (“M4”) cell lines. We have previously shown that tumor suppressor activity of TGF-beta is lost in the highly malignant M4 cells. To determine how the spectrum of TGF-beta-regulated genes changes with cancer progression, we performed gene expression array analysis on four cell lines of the MCF10A-based model of breast cancer progression (M1-M4) cultured in vitro under serum-free conditions and treated with TGF-beta (5ng/ml plus condition) or vehicle (minus condition) for 1h or 6h.
2015-01-01 | GSE34270 | GEO
Project description:Transforming growth factor beta-1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGFbeta (0.4 ng/ml), or double-treated. All double-treated (IR+TGFbeta) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, beta-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFbeta alone elicited EMT, even though IR increased chronic TGFbeta signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGFbeta-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGFbeta, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression. Keywords: response to ionizing radiation, response to transforming growth factor-beta, nonmalignant human mammary epithelial MCF10A cells, epithelial to mesenchymal transition
2007-06-25 | GSE8240 | GEO
Project description:Breast carcinoma (BRCA) has emerged as the leading cancer worldwide with the highest incidence. The malignant transformation of normal breast epithelial cells is a crucial prerequisite for the initiation of breast cancer. However, the underlying epigenomic mechanism remains poorly understood. Here, we utilized guide positioning sequencing (GPS) to conduct whole-genome DNA methylation analysis in an MCF10 series of cell lines, a typical model of malignant progression including normal breast epithelial MCF10A, premalignant MCF10AT, low-grade metastatic MCF10CA1h, and high-grade metastatic MCF10CA1a. By integrating mRNA-seq with matched clinical data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), six representative methylation-related differentially expressed genes (mrDEGs) were screened, including CAVIN2, ARL4D, DUSP1, TENT5B, P3H2, and MMP28. To mimic tumor progression in vitro, we independently optimized and employed the site-specific dCas9-DNMT3L-DNMT3A system to artificially downregulate TENT5B in MCF10A cells, demonstrating that transcriptional silence of TENT5B accelerates cell proliferation in MCF10A cells owing to the crosstalk between hypermethylation and histone deacetylation. Our data highlight the practical implications of DNA methylation dynamics in reshaping epigenomic features during the BRCA malignant progression. The site-specific methylation technique would help gain a comprehensive understanding of pathogenic mechanisms and facilitate future therapeutic approaches in epigenome editing.
2025-01-29 | GSE267744 | GEO
Project description:ChIP-Seq was performed on naiive cell lines from a Breast Cancer Progression model, including MCF10A, MCF10AT1, and DCIS. Biological replicates (n=2) were performed for all factors across all cell lines described.
2022-03-07 | GSE197960 | GEO
Project description:Transforming growth factor beta-1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGFbeta (0.4 ng/ml), or double-treated. All double-treated (IR+TGFbeta) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, beta-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFbeta alone elicited EMT, even though IR increased chronic TGFbeta signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGFbeta-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGFbeta, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression. Experiment Overall Design: Nonmalignant human mammary epithelial MCF10A cells (passages 106 and 108) were seeded at cloning density in 35mm dishes (10^5 cells/dish). Cell culture medium consisted of 3ml/dish of MGEM serum free medium (Cambrex Inc.), supplemented or not with 400pg/ml recombinant Transforming Growth Factor-beta. Cells were irradiated or not 5h post plating using 160 KV X-ray with a total dose of 2Gy. Sham, IR-treated, TGFbeta-treated and double-treated (IR+TGFbeta) MCF10A cells were harvested 8 days post-IR. Briefly, cells were washed with PBS, denatured in Trizol, scraped off the dish and subjected to chloroform extraction. After centrifugation, the upper phase was precipitated with an equal volume of isopropanol. RNA precipitates were resuspended in RNase free water and further purified on RNeasy columns (Qiagen, Germany). RNA quality was assessed on an Agilent Bio-Analyzer. The dataset analyzed by microarray included biological duplicates for each treatment in two independent experiments and three sham treated samples. Microarray data were generated at the Lawrence Berkeley National Laboratory Molecular Profiling Laboratory (http://hta.lbl.gov) using a high-throughput, automated GeneChip system (Affymetrix). Briefly, target preparation, HT_HG-U133A array plate hybridization setup, washing and staining were performed on an Affymetrix robotic system (GCAS) using version 2.1 protocols. Scanning (protocol version 2.2.09) was performed on a CCD-based high throughput scanner (Affymetrix). Samples were analyzed and clustered with the (UNO) One Color GenetrafficTM software version 3.2-12 (Iobion Informatics LLC, Stratagene, La Jolla, CA). Genes whose expression was specifically altered by treatment were defined as those in which dye ratio was more than 1.75-fold (|mean log2ratio|>0.8) from baseline in at least three out of the four treated samples compared to the three sham samples. Significance analysis tests (p<0.05) were performed using Excel between sham samples and either IR, TGFbeta or TGFbeta+IR samples.
2008-11-08 | E-GEOD-8240 | biostudies-arrayexpress
Project description:With this experiment, we aimed to decipher the epigenetic changes occuring during tumour progression in a model of basal-like breast cancer, based on immortalized mammary epithelial cells (IMEC). The tumorigenic IMEC, xenograft-derived and metastasis-derived cells were used for the analysis
2024-02-02 | GSE211606 | GEO
Project description:MCF10A series is one of the few human models of breast tumor progression. A derivative of MCF10A cells is the MCFDCIS, which reproducibly forms comedo DCIS-like lesions that spontaneously progress to invasive tumors. We used this model to explore the relative importance of myoepithelial cells and stromal fibroblasts in the in situ to invasive breast carcinoma transition. We use Affymetrix 11K XbaI or 250K StyI SNP arrays to analyze the MCF10A series cells and MCFDCIS derived xenografts for copy number changes and LOH (loss of heterozygosity). Keywords: Cell line, xenografts of time course/co-injection groups, different cell types isolated from xenografts
2008-03-07 | GSE10747 | GEO
Project description:With this experiment, we aimed to decipher the changes in chromatin accessibility during tumour progression in a model of basal-like breast cancer, based on immortalized mammary epithelial cells (IMEC). The tumorigenic IMEC, xenograft-derived and metastasis-derived cells were used for the analysis
2024-02-02 | GSE211605 | GEO
Project description:TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. Our goal was to use integrated genomic approaches in a model of human breast cancer progression to identify core TGF-beta-regulated genes that specifically reflect the tumor suppressor activity of TGF-beta. The model consisted of the non-tumorigenic MCF10A (“M1”), the premalignant MCF10AT1k.cl2 (“M2”), the early malignant MCF10Ca1h (“M3”) and the highly malignant, metastatic MCF10Ca1a.cl1 (“M4”) cell lines. We have previously shown that tumor suppressor activity of TGF-beta is dependent on Smad3, and is lost in M4 cells. To identify how TGF-beta/Smad3 targets change with cancer progression, we performed promoter-wide Smad3 ChIP-chip on all four cell lines of the breast cancer progression model (M1-M4), following treatment with TGF-beta or vehicle control.
2015-01-01 | GSE34271 | GEO