Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA188105 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identification of p130Cas/ErbB2-dependent invasive signatures in transformed mammary epithelial cells
| PRJNA183933 | ENA
Project description:Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is over-expressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas over-expression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiling, we define the invasive signatures associated with concomitant p130Cas over-expression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amminoacids synthesis (CBS and PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are up-regulated while genes involved in the inflammatory response (SAA1, S100A7) are down-regulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, mir-200b, miR-222, miR-221and miR-424 are up-regulated while miR-27a, miR-27b and miR-23b are down-regulated. Overall this study present, for the first time, gene expression changes underlying the invasive behaviour following p130Cas over-expression in an ErbB2 transformed mammary cell model. 12 samples were analyzed: 3 ErbB2, 3 Cas, 3 Cas/ErbB2, 3 Ctr MCF10A.B2
2013-08-01 | E-GEOD-43907 | biostudies-arrayexpress
Project description:Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model. To identify transcriptional changes occurring during invasion we have performed a comparative microarray analysis of non coding RNA (miRNA) between MCF10A.B2 acini over-expressing p130Cas with activation of ErbB2 and control cells.
2013-07-22 | E-GEOD-42949 | biostudies-arrayexpress
Project description:Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is over-expressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas over-expression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiling, we define the invasive signatures associated with concomitant p130Cas over-expression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amminoacids synthesis (CBS and PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are up-regulated while genes involved in the inflammatory response (SAA1, S100A7) are down-regulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, mir-200b, miR-222, miR-221and miR-424 are up-regulated while miR-27a, miR-27b and miR-23b are down-regulated. Overall this study present, for the first time, gene expression changes underlying the invasive behaviour following p130Cas over-expression in an ErbB2 transformed mammary cell model.
2013-08-01 | GSE43907 | GEO
Project description:Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model.
2013-07-22 | GSE42949 | GEO
Project description:The mechanisms of ErbB2 signalling and the effects of its overexpression are not fully understood. Herein, SILAC expression profiling and phosphopeptide enrichment of a relevant, non-transformed, immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGFR (EGF treatment) and ErbB3 (HRGbeta1 treatment) in the context of ErbB2 overexpression. Bioinformatics analysis was used to infer changes in cellular processes and signalling events. We demonstrate the complexity of the responses to oncogene expression and growth factor signalling and identify protein changes relevant to ErbB2-dependent altered cellular phenotype, in particular cell cycle progression and hyper-proliferation, reduced adhesion and enhanced motility. Numerous novel sites of growth factor-regulated phosphorylation were also identified that were enhanced by ErbB2 overexpression and we putatively link these to altered cell behaviour. Moreover, we have defined a novel mechanism by which ErbB signalling suppresses basal interferon signalling that would promote the survival and proliferation of mammary luminal epithelial cells.
2018-10-26 | PXD004195 | Pride
Project description:Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB2 and indeed enhances invasiveness triggered by ErbB2. We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation.
2014-03-01 | GSE55042 | GEO
Project description:Understanding changes in gene expression during tumor initiation and progression is critical to understanding how genetic alterations drive malignancy. We used a genetically defined cell culture model to study the progression of normal human mammary epithelial cells (HMECs) to malignancy. Primary HMECs were immortalized through the expression of hTERT, p53DD, cyclin D1, CDK4R24C and c-MYCT58A. This immortalization conferred limitless replicative potential as well as migratory capacity. These pre-malignant cells were subsequently HRASG12V transformed, which converted the immortalized cells to a fully tumorigenic state with significantly increased invasive capacity. We analyzed the cells using RNA-sequencing, and we report dramatic mRNA expression changes during the pre-malignant immortalization of primary cells, and very few mRNA expression changes occurring during oncogenic Ras transformation. RNA signatures in pre-malignant immortalized and Ras-transformed cells are consistent with previously reported epithelial-to-mesenchymal transition (EMT) signatures.
2018-05-25 | GSE110677 | GEO
Project description:We have previously shown that transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor development in MTB-IGFIR mice. In this study we evaluated whether the miR-200b/200a/429 cluster could also prevent mammary tumor development from a different oncogene, namely Neu/Erbb2. We found that transgenic overexpression of Neu/Erbb2 in MTB-TAN mice induce rapid mammary tumor development and co-overexpression of the miR-200b/200a/429 cluster with Neu/Erbb2 completely prevent mammary epithelial transformation and tumor development
2024-08-26 | GSE270979 | GEO
Project description:Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB2 and indeed enhances invasiveness triggered by ErbB2. We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation. genome-wide human SNP 6.0 arrays from Affymetrix was used to determine the copy number changes of MCF10A cells with extra centrosomes or depleted of MCAK after grown 4 days in 3-D cultures
2014-03-01 | E-GEOD-55042 | biostudies-arrayexpress