Pten signaling in fibroblasts effects gene expression in endothelial and epithelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE24501 | GEO | 2011/12/18
SECONDARY ACCESSION(S): PRJNA132605
REPOSITORIES: GEO
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Project description:These experiments aim determine the effects of Pten signaling in fibroblasts on gene expression in other cell compartments in the mammary gland. To achieve this, we used a genetic model in which the tumor suppressor gene Pten was specifically inactivated in stromal fibroblats. We then isolated fibroblasts, epithelial cells and endothelial cells from the mammary glands of mice with either wild type or Pten null fibroblasts. Comparisons were made between wild type and Pten counterparts, not between the various cell types.
2011-12-18 | E-GEOD-24501 | biostudies-arrayexpress
Project description:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor roles are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients Wild type. PtenF341V, PtenWT/null, and Pten null CDH1 positive epithelials cells of mammary ducts from 8 week old female mice were isolated by FACS, RNA was extracted and Affymetrix gene expression arrays were performed.
2014-12-19 | E-GEOD-64303 | biostudies-arrayexpress
Project description:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor roles are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients
2014-12-19 | GSE64303 | GEO
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 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.
2009-10-22 | GSE16073 | GEO
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:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor mechanisms are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN that differentially alter the Akt axis in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation. These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients Wild type, Pten null and PtenF341V primary mouse embryonic fibroblasts isolated from 13.5 day old embryos (E13.5) were cultured, RNA was extracted and Affymetrix gene expression arrays were performed.
2014-12-19 | E-GEOD-64302 | biostudies-arrayexpress
Project description:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor mechanisms are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN that differentially alter the Akt axis in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation. These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients
2014-12-19 | GSE64302 | GEO
Project description:Mammary epithelial cells (MECs), the only cell type which could be capable of secreting milk in mammary gland, can be applied for the generation of transgenic mammary cell/gland bioreactor. However, continuously achieving large amount of high-quality goat MECs by non-invasion method, especially prepuberal MECs, in vitro has been a challenge. Here, we show that a small molecules cocktail enables the in vitro generation of chemically-induced mammary epithelial cells (CiMECs) with milk-secreting properties from goat ear fibroblasts. The properties of CiMECs were highly similar to those of naturally isolated MECs. Notably, the CiMECs lineage reprogramming process may partially imitate the MECs developmental process from embryonic to milk-secreting stages. Interestingly, fibroblasts were firstly reversed back to embryonic ectoderm/surface ectoderm-like state. Our findings constitute a substantial step toward further promoting the application of transgenic mammary bioreactors, moreover, also offer a new strategy for obtaining other cell types by reprogrammed fibroblasts.
2022-12-20 | GSE142550 | GEO
Project description:Mammary epithelial cells (MECs), the only cell type which could be capable of secreting milk in mammary gland, can be applied for the generation of transgenic mammary cell/gland bioreactor. However, continuously achieving large amount of high-quality goat MECs by non-invasion method, especially prepuberal MECs, in vitro has been a challenge. Here, we show that a small molecules cocktail enables the in vitro generation of chemically-induced mammary epithelial cells (CiMECs) with milk-secreting properties from goat ear fibroblasts. The properties of CiMECs were highly similar to those of naturally isolated MECs. Notably, the CiMECs lineage reprogramming process may partially imitate the MECs developmental process from embryonic to milk-secreting stages. Interestingly, fibroblasts were firstly reversed back to embryonic ectoderm/surface ectoderm-like state. Our findings constitute a substantial step toward further promoting the application of transgenic mammary bioreactors, moreover, also offer a new strategy for obtaining other cell types by reprogrammed fibroblasts.
2022-12-20 | GSE142549 | GEO