Expression Data from Pten Null Fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE16073 | GEO | 2009/10/22
SECONDARY ACCESSION(S): PRJNA115499
REPOSITORIES: GEO
Similar Datasets
Project description:The tumor stroma is believed to contribute to some of the most malignant characteristics of epithelial tumors. However, signaling between stromal and tumor cells is complex and remains poorly understood. Here we show that genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumors. Global gene expression profiling in mammary stromal cells identified a Pten-specific signature associated with massive extra-cellular matrix (ECM) remodeling, innate immune cell infiltraion and increased angiogenesis. Execution of this transcriptional program was mediated, in part, by the induction, phosphorylation and recruitment of Ets2 to target promoters. Remarkably, Ets2 inactivation in Pten stroma-deleted tumors was sufficient to decrease tumor growth and progression. These findings identify the Pten-Ets2 axis as a critical stroma-specific signaling pathway that suppresses mammary epithelial tumors. Experiment Overall Design: Wild type and Pten null primary mammary fibroblasts isolated from 8 week old female mice were cultured, RNA was extracted and Affymetrix gene expression arrays were performed.
2009-11-10 | E-GEOD-16073 | biostudies-arrayexpress
Project description:The mechanisms involved in epithelium-stroma interactions remain poorly understood, despite the importance of the microenvironment during tumorigenesis. Here, we studied the role of Ets2 transcrpiton factor in tumor associated fibroblasts in the MMTV-ErbB2 mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor growth, in contrast to Ets2 inactivation in epithelium in which no differences in tumor growth were observed. Microarray analysis on isolated fibroblasts demonstrated the important role of Ets2 in remodeling of the extracellular matrix and angiogenesis in these cells. Tumors lacking Ets2 in fibroblats had diminished blood vessels. Our tumor specific gene signature was also represented in the stroma of human breast cancer patients. Collectively, our results suggest Ets2 uniquely contributes to angiogenesis from fribroblasts in the tumor microenvironment. Primary mammary fibroblasts were isolated from mice with no oncogene with or without Ets2 and with the ErbB2 oncogene with or without Ets2, RNA was extracted and samples were submitted for Affymetrix gene expression arrays
2013-12-01 | E-GEOD-44166 | biostudies-arrayexpress
Project description:The mechanisms involved in epithelium-stroma interactions remain poorly understood, despite the importance of the microenvironment during tumorigenesis. Here, we studied the role of the Ets2 transcription factor in tumor-associated fibroblasts in the MMTV-PyMT mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor growth, in contrast to Ets2 inactivation in epithelium, in which no differences in tumor growth were observed. Microarray analysis on isolated fibroblasts demonstrated the important role of Ets2 in remodeling of the extracellular matrix and angiogenesis in these cells. At the molecular level, Ets2 regulated Mmp9 expression through direct binding to the promoter region. Tumors lacking Ets2 in fibroblasts had diminished blood vessels. We also found a significant correlation between phosphorylation of ETS2 and MMP9 levels in stroma of human breast cancer samples. Collectively, our results suggest Ets2 uniquely contributes to angiogenesis from fibroblasts in the tumor microenvironment. Primary mammary fibroblasts were isolated from mice without the PyMT oncogene with or without Ets2, and from mice with the PyMT oncogene with or without Ets2. RNA was extracted and samples were submitted for Affymetrix gene expression arrays.
2014-03-19 | E-GEOD-16989 | biostudies-arrayexpress
Project description:The mechanisms involved in epithelium-stroma interactions remain poorly understood, despite the importance of the microenvironment during tumorigenesis. Here, we studied the role of Ets2 transcrpiton factor in tumor associated fibroblasts in the MMTV-ErbB2 mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor growth, in contrast to Ets2 inactivation in epithelium in which no differences in tumor growth were observed. Microarray analysis on isolated fibroblasts demonstrated the important role of Ets2 in remodeling of the extracellular matrix and angiogenesis in these cells. Tumors lacking Ets2 in fibroblats had diminished blood vessels. Our tumor specific gene signature was also represented in the stroma of human breast cancer patients. Collectively, our results suggest Ets2 uniquely contributes to angiogenesis from fribroblasts in the tumor microenvironment.
2013-12-01 | GSE44166 | GEO
Project description:The mechanisms involved in epithelium-stroma interactions remain poorly understood, despite the importance of the microenvironment during tumorigenesis. Here, we studied the role of the Ets2 transcription factor in tumor-associated fibroblasts in the MMTV-PyMT mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor growth, in contrast to Ets2 inactivation in epithelium, in which no differences in tumor growth were observed. Microarray analysis on isolated fibroblasts demonstrated the important role of Ets2 in remodeling of the extracellular matrix and angiogenesis in these cells. At the molecular level, Ets2 regulated Mmp9 expression through direct binding to the promoter region. Tumors lacking Ets2 in fibroblasts had diminished blood vessels. We also found a significant correlation between phosphorylation of ETS2 and MMP9 levels in stroma of human breast cancer samples. Collectively, our results suggest Ets2 uniquely contributes to angiogenesis from fibroblasts in the tumor microenvironment.
2014-03-19 | GSE16989 | GEO
Project description:Tissue of the breast is heterogeneous, consisting of a variety of cell types and connective tissue. This heterogeneity is also present in breast tumors and will complicate proteomic analysis, as it is not always clear whether a signal originates from the stromal environment, from normal epithelial or tumor cells. Here we microdissected a variety of cell types and stroma from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Although this heterogeneity complicated detection of differentially abundant proteins, several markers were exclusively detected in stroma. However, as heterogeneity in the stroma is more difficult to be reduced through microdissection, comparative analysis was most informative in microdissected cells of epithelial origin, and provided a relatively complete picture of malignant transformations.
2017-01-11 | PXD003632 | Pride
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways. Experiment Overall Design: Common reference design. 9 samples (including 2 normal tissue and 7 tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.
2009-07-03 | E-GEOD-13916 | biostudies-arrayexpress
Project description:Fibroblasts within the mammary tumor microenvironment are active participants in carcinogenesis mediating both tumor initiation and progression. Our group has previously demonstrated that genetic loss of PTEN in mammary fibroblasts induces an oncogenic secretome that remodels the extracellular milieu accelerating ErbB2-driven mammary tumor progression. While these prior studies highlighted a tumor suppressive role for stromal PTEN, how the adjacent normal epithelium transforms in response to PTEN loss was not previously addressed. To identify these early events, we have evaluated both phenotypic and genetic changes within the pre-neoplastic mammary epithelium of mice with and without stromal PTEN expression. We report that fibroblast-specific PTEN deletion greatly restricts mammary ductal elongation and induces aberrant alveolar side-branching. These mice concomitantly exhibit an expansion of the mammary epithelial stem cell (MaSC) enriched basal/myoepithelial population and further genome wide expression analysis followed by gene set enrichment analysis (GSEA) revealed that NOTCH signaling is diminished in these cells. NOTCH3 was confirmed to be downregulated in the MaSC-enriched pool by confirmatory qRT-PCR and immunofluorescence. Mechanistically, JAGGED-1, a transmembrane ligand for the NOTCH receptor, is downregulated in the PTEN-null fibroblasts leading to a loss in the paracrine activation of NOTCH signaling from the surrounding stroma.
2016-09-09 | GSE84190 | GEO
Project description:Previously we have demonstrated that inactivation of retinoic acid receptor beta (Rarb) in the mouse results in a protective effect against ErbB2-induced mammary gland tumorigenesis although Rarb has been reported as a tumor suppressor before. In the current study, we further confirmed that ablation of Rarb has a very similar impact on Wnt1-induced mammary gland tumorigenesis as those on ErbB2-induced mammary gland tumorigenesis. Nevertheless, the mechanisms by which Rarb confers its effects on tumor progression is quite different although both involving in tumor microenvironment (TME) remodeling. In the Wnt1 tumors, ectopic wnt1 produced by malignant luminal cells activates nearby stromal cells by a paracrine manner. In return, the stromal cells secreted IGF1 to regulate the growth of tumor cells. There is a need of Rarb expression in this interaction. Deletion of Rarb inhibits both wnt1/β-catenin signaling and IGF1/Akt axis in the myoepithelial tumor cells which results in the suppression of epithelial-mesenchymal transition (EMT) in these tumors. Since wnt1 tumors resemble basal-like breast cancer with a poor clinical prognosis in which EMT is one of the most important way for tumor cells to survive against standard treatment and to go to metastasis, we propose that (1) the stromal gene expression signature of Rarb ablation in wnt1 tumors could have some clinical value in predicting the breast cancer outcome; and (2) Rarb antagonist might be a potential therapeutic strategy in EMT-driven aggressive cancers such as basal-like breast cancer. Laser capture microdissection (LCM) was performed to separate the mammary tumor samples into epithelial cell compartment and stromal cell compartment. Transcriptional profiling of the two compartments were investigated by microarray analysis.
2014-10-23 | E-GEOD-56391 | biostudies-arrayexpress
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways.
2009-06-29 | GSE13916 | GEO