Expression Data from Endothelial Cells as a Consequence of Ets2 Signaling in PyMT Tumor Associated Fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE44118 | GEO | 2013/12/01
SECONDARY ACCESSION(S): PRJNA188714
REPOSITORIES: GEO
Similar Datasets
Project description:Tumor associated fibroblasts are known to play an important role in angiogenesis, however the specific signaling pathways playing an important role in this cross talk remain ill defined. Here, we studied how Ets2 transcrpiton factor signaling in tumor associated fibroblasts effected gene expression in surrounding endothelial cells in the MMTV-PyMT mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor associated angiogenesis, and was indicated to effect ECM remodeling, cell adhesion and cell chemotaxis processes in neighboring endothelial cells. We have identified Ets2 in fibroblasts as a key signaling molecule to induce tumor associated angiogenesis. Additionally, this function does not rely on the presence of tumor cells, indicating a memory in fibroblasts to induce angiogenesis. Primary mammary endothelial cells were isolated from mice with or without fibroblast Ets2 in the presence of the PyMT oncogene through sorting with a CD31 antibody. RNA was extracted and samples were submitted for Affymetrix gene expression arrays
2013-12-01 | E-GEOD-44118 | 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.
2014-03-19 | GSE16989 | 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 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 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. 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:Macrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes. Activation of this transcriptional program correlated with decreased angiogenesis in metastatic tumors and decreased metastatic growth. Comparison of this Ets2-specific TAM expression profile with human breast cancer profiles revealed a macrophage gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung.
2010-01-05 | GSE12863 | GEO
Project description:Macrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes. Activation of this transcriptional program correlated with decreased angiogenesis in metastatic tumors and decreased metastatic growth. Comparison of this Ets2-specific TAM expression profile with human breast cancer profiles revealed a macrophage gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung. Breast TAMs were isolated from early-stage PyMT-induced mammary tumors expressing Ets2 and also from the tumors with Ets2-deficient TAMs. Since macrophages have also been implicated in normal mammary gland remodeling, normal remeodeling macrophages were also purified from females expressing Ets2 and the ones where Ets2 is deleted in the macrophages. One RNA sample was extracted from each genetic group for gene-expression profiling.
2010-01-05 | E-GEOD-12863 | biostudies-arrayexpress
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:Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate the activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes. This genomic data, and an ETS1 deletion line are used to show that the opposite function of ETS2 is due to binding site competition and a weaker activation function of ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor BS69 (ZMYND11). Gene expression data from tumor cohorts was then used to show that BS69 expression level in tumors correlates with oncogenic and tumor suppressive roles of ETS2. Therefore, these data indicate a novel and specific mechanism allowing ETS2 to switch between oncogenic and tumor suppressive functions in a cell-type specific manner.
2017-02-13 | GSE86239 | GEO
Project description:Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate the activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes. This genomic data, and an ETS1 deletion line are used to show that the opposite function of ETS2 is due to binding site competition and a weaker activation function of ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor BS69 (ZMYND11). Gene expression data from tumor cohorts was then used to show that BS69 expression level in tumors correlates with oncogenic and tumor suppressive roles of ETS2. Therefore, these data indicate a novel and specific mechanism allowing ETS2 to switch between oncogenic and tumor suppressive functions in a cell-type specific manner.
2017-02-13 | GSE86238 | GEO