Comparing breast tumor cell-induced gene expression in primary mammary fibroblasts from MEKK1-deficient mice to fibroblasts from MEKK1+/+ mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA703037 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:p53 is a known tumor suppressor. We have found that stromal p53 regulates breast cancer development, the immune landscape, and survival in an oncogene specific manner when comparing the epithelial oncogenes ErbB2 and KrasG12D In this dataset, we have evaluated mammary epithelia from mice with and without epithelial KrasG12D and with and without stromal p53 deletion. We have also evaluated mammary fibroblasts from mice with and without epithelial KrasG12D and with and without stromal p53 deletion.
2022-05-01 | GSE201935 | GEO
Project description:To investigate the impact of combined Rb and p53 loss in mammary tumorigenesis, we used transgenic and viral approaches to delete Rb and p53 floxed alleles specifically in the mouse mammary epithelium. Although MMTV-Cre (NLST) targets stem/bi-potent progenitors in the mammary gland, a subset of MMTV-Cre:Rbf/f;p53f/f mice developed non-mammary tumors. Thus, freshly isolated primary mammary epithelial cells from these animals were transplanted into the mammary fat pads of immunodeficient mice and monitored for tumor formation. In addition, primary MECs were isolated from Cre-negative Rbf/f;p53f/f mice, infected with Ad-Cre followed by orthotopic transplantation. In all these cases, resulting tumors shared similar spindle-shape histology, expressed high levels of vimentin, a mesenchymal marker, but not E-cadherin, a luminal marker, and were classified as adeno-sacrcomatoid/spindle-cell/mesenchymal-like breast cancer. We used microarrays to detect differentially expressed genes in the Rb/p53 double-knock-out vs p53 single deletion or normal mammary tissue.
2014-10-03 | GSE62016 | GEO
Project description:This study examined the importance of intracellular kinase MEKK1 in breast tumor-induced on gene expression in non-tumor mammary cells. The hypothesis tested in this study was that the kinase MEKK1 regulates breast tumor cells-induced expression of fibroblast genes that change the tumor microenvironment to promote breast tumor progression to metastasis. Results reveal that MEKK1 regulates expression of chemokines and other genes in normal breast stroma cells that contribute to the development of a tumor microenvironment that promotes metastasis.
2021-02-20 | GSE167130 | GEO
Project description:To investigate the impact of combined Rb and p53 loss in mammary tumorigenesis, we used transgenic and viral approaches to delete Rb and p53 floxed alleles specifically in the mouse mammary epithelium. Although MMTV-Cre (NLST) targets stem/bi-potent progenitors in the mammary gland, a subset of MMTV-Cre:Rbf/f;p53f/f mice developed non-mammary tumors. Thus, freshly isolated primary mammary epithelial cells from these animals were transplanted into the mammary fat pads of immunodeficient mice and monitored for tumor formation. In addition, primary MECs were isolated from Cre-negative Rbf/f;p53f/f mice, infected with Ad-Cre followed by orthotopic transplantation. In all these cases, resulting tumors shared similar spindle-shape histology, expressed high levels of vimentin, a mesenchymal marker, but not E-cadherin, a luminal marker, and were classified as adeno-sacrcomatoid/spindle-cell/mesenchymal-like breast cancer. We used microarrays to detect differentially expressed genes in the Rb/p53 double-knock-out vs p53 single deletion or normal mammary tissue. Total RNA was extracted from tumors developed by double Trizol method and hybridized on Affymetrix microarrays
2014-10-03 | E-GEOD-62016 | biostudies-arrayexpress
Project description:The Th-inducing POK (Th-POK, also known as cKrox or ZBTB7B) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. We found that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands. Th-POK is not required for mammary gland development in puberty and alveologenesis in pregnancy. Th-POK-deficient mice are defective in secretory activation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. We compared microarray gene expression in mammary glands of lactating wild-type or Th-POK-deficient mice. We show that Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the mammary glands. Thus, Th-POK function as an important regulator of insulin signaling in mammary gland lactation.
2018-02-06 | GSE97566 | GEO
Project description:<p><strong>INTRODUCTION:</strong> A decline in mitochondrial function represents a key factor of a large number of inborn errors of metabolism, which lead to an extremely heterogeneous group of disorders.</p><p><strong>OBJECTIVES:</strong> To gain insight into the biochemical consequences of mitochondrial dysfunction, we performed a metabolic profiling study in human skin fibroblasts using galactose stress medium, which forces cells to rely on mitochondrial metabolism.</p><p><strong>METHODS:</strong> Fibroblasts from controls, complex I and pyruvate dehydrogenase (PDH) deficient patients were grown under glucose or galactose culture condition. We investigated extracellular flux using Seahorse XF24 cell analyzer and assessed metabolome fingerprints using NMR spectroscopy.</p><p><strong>RESULTS:</strong> Incubation of fibroblasts in galactose leads to an increase in oxygen consumption and decrease in extracellular acidification rate, confirming adaptation to a more aerobic metabolism. NMR allowed rapid profiling of 41 intracellular metabolites and revealed clear separation of mitochondrial defects from controls under galactose using partial least squares discriminant analysis. We found changes in classical markers of mitochondrial metabolic dysfunction, as well as unexpected markers of amino acid and choline metabolism. PDH deficient cell lines showed distinct upregulation of glutaminolytic metabolism and accumulation of branched-chain amino acids, while complex I deficient cell lines were characterized by increased levels in choline metabolites under galactose.</p><p><strong>CONCLUSION:</strong> Our results show the relevance of selective culture methods in discriminating normal from metabolic deficient cells. The study indicates that untargeted fingerprinting NMR profiles provide physiological insight on metabolic adaptations and can be used to distinguish cellular metabolic adaptations in PDH and complex I deficient fibroblasts.</p>
2021-10-06 | MTBLS761 | MetaboLights
Project description:Primary mammary gland stromal fibroblasts from pubertal SHARPIN-deficient cpdm/cpdm -mice and their littermate controls
2016-12-15 | GSE83795 | GEO
Project description:Shotgun proteomics data comparing basal mammary cellular population obtained from wild-type and timp knockout mice.
2014-07-15 | MSV000078779 | MassIVE
Project description:Mammary fibroblasts (CD1 strain of mouse) that were exposed to BPA or oil control in utero were isolated from 12 week old mice. RNA was harvested and sequenced from the fibroblasts.
2019-08-21 | GSE136062 | GEO
Project description:Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state, as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. Comparison of tissue proteomics data with all those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1 and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.
2014-09-23 | PXD001311 | Pride