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
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.
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.
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
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.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.