Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-32129
PROVIDER: PRJNA147437 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mammary organoids harvested from ErbB3 DOX-KO mice, which utilize MMTV-Cre transgene expression in the LE to cause genomic recombination at floxed ErbB3 alleles in ErbB3FL/FL were cultured in the presence or absence of doxycycline to induce ErbB3 loss. The gene expression shift following DOX-induced ErbB3 loss in the 3D organoids was examined by microarray. Gene expression patterns were interrogated in mammary organoids from ErbB3 inducible-knockout mice cultured in the presence of absence of doxycycline. Three biological replicates of the experiment were performed, resulting in a total of 6 samples (3 treatment, 3 control).
2012-01-04 | E-GEOD-32129 | biostudies-arrayexpress
Project description:Mammary organoids harvested from ErbB3 DOX-KO mice, which utilize MMTV-Cre transgene expression in the LE to cause genomic recombination at floxed ErbB3 alleles in ErbB3FL/FL were cultured in the presence or absence of doxycycline to induce ErbB3 loss. The gene expression shift following DOX-induced ErbB3 loss in the 3D organoids was examined by microarray.
2012-01-04 | GSE32129 | GEO
Project description:In this experiment, we have tested the effect of microRNA-203 as a potential differentiation inducer in breast cancer organoids, derived from the PyMT mouse model. MMTV-PyVT transgenic mice express the Polyoma Virus middle T antigen under the direction of the mouse mammary tumor virus promoter/enhancer. Hemizygous MMTV-PyMT females develop palpable mammary tumors which metastasize to the lung. These mice have high penetrance of early onset of mammary cancer compared to other mammary tumor models. PyMT mice were crossed with miR-203 knock-in mice, where miR-203 expression is induced upon DOX treatment. Thus, organoids derived from the mammary gland tumors of such mouse model where evaluated in vitro. miR-203 expression was therefore induced by Doxycycline in vitro, and compared to other well-defined differentiation media for breast cancer tissue, such as the mammary epithelial cell culture media and kit (CC-2551B; Lonza).
2023-08-09 | GSE202831 | GEO
Project description:Mutations in PIK3CA, the gene encoding the p110α subunit of PI3K, induce transformation of mammary epithelial cells (MEC). Studies suggest the transforming action of mutant PIK3CA requires binding to activated receptor tyrosine kinases or adaptors. We examined in transgenic mice if ErbB3, a powerful activator of PI3K, is required for mutant PIK3CA-mediated MEC transformation. ErbB3 loss delayed PIK3CAH1047R-dependent mammary gland hyperplasia, but tumor latency, gene expression and markers of PI3K signaling were unaffected. In ErbB3-deficient tumors, mutant PI3K remained associated with other tyrosine phosphorylated adaptors, potentially explaining the dispensability of ErbB3 for tumorigenicity and PI3K activity. Combined inhibition of ErbB RTKs and PI3K with lapatinib and the p110α inhibitor BYL719, respectively, reduced PIK3CAH1047R-dependent tumor growth and PI3K signaling more potently than the p110α inhibitor alone. In human breast cancer cells harboring PIK3CAH1047R, the combination with BYL719 and an ErbB3 inhibitor synergistically inhibited tumor growth and P-Akt. These data suggest that basal tumor growth and PI3K signaling do not depend on ErbB RTKs in PIK3CAH1047R-expressing tumors. However, upon inhibition of p110α, these receptors limit the action of PI3K inhibitors potentially explaining the more potent effect of the combination against PI3K-mutant cancers. reference x sample
2013-06-20 | E-GEOD-43037 | biostudies-arrayexpress
Project description:The WWOX gene has been implicated in human cancers, including breast cancer.The development and tumorigenesis between human and mouse mammary glands (MGs) share similar molecular details and signal transduction pathways. We established mouse line that specifically knockout the expression of WWOX gene in the MG epithelial cells (MECs) by crossing BK5-cre mice with our WWOX flox stain. In order to study the gene expression profile in the subpopulation MECs, we isolated the organoids from the 4th MGs of both BK5-cre +; WWOX flox/flox (KO) mice and their WT counterparts (BK5-cre -; WWOX flox/flox), 3 mice each genotype. The total RNA from the mouse MG organoids was extracted and purified by TRIzol/RNeasy Kit and their integrity was checked on Agilent RNA 6000 Nanochip. The goal is to identify the significant perturbation in tumorigenic pathways in these cells induced by WWOX ablation. Mammary gland epithelial organoids samples and gene expression profiles were deribed from three WWOX-KO mice (BK5-cre +; WWOX flox/flox) and from three WWOX-WT mice (BK5-cre -; WWOX flox/flox)
2012-04-14 | E-GEOD-36665 | biostudies-arrayexpress
Project description:Mutations in PIK3CA, the gene encoding the p110α subunit of PI3K, induce transformation of mammary epithelial cells (MEC). Studies suggest the transforming action of mutant PIK3CA requires binding to activated receptor tyrosine kinases or adaptors. We examined in transgenic mice if ErbB3, a powerful activator of PI3K, is required for mutant PIK3CA-mediated MEC transformation. ErbB3 loss delayed PIK3CAH1047R-dependent mammary gland hyperplasia, but tumor latency, gene expression and markers of PI3K signaling were unaffected. In ErbB3-deficient tumors, mutant PI3K remained associated with other tyrosine phosphorylated adaptors, potentially explaining the dispensability of ErbB3 for tumorigenicity and PI3K activity. Combined inhibition of ErbB RTKs and PI3K with lapatinib and the p110α inhibitor BYL719, respectively, reduced PIK3CAH1047R-dependent tumor growth and PI3K signaling more potently than the p110α inhibitor alone. In human breast cancer cells harboring PIK3CAH1047R, the combination with BYL719 and an ErbB3 inhibitor synergistically inhibited tumor growth and P-Akt. These data suggest that basal tumor growth and PI3K signaling do not depend on ErbB RTKs in PIK3CAH1047R-expressing tumors. However, upon inhibition of p110α, these receptors limit the action of PI3K inhibitors potentially explaining the more potent effect of the combination against PI3K-mutant cancers.
2013-06-20 | GSE43037 | GEO
Project description:Purpose: The goals of this study are to compare mammary tumor transcriptome profiling with or without DDR1 in immunocompetent mice in an unbiased way. Methods: In vitro samples: DDR1 WT or KO in vitro cultured E0771 cells were sequenced. Rag1-/- samples: DDR1 WT or KO E0771 cells were injected in Rag1-/- mice, and tumors were harvested and sequenced. C57BL/6 samples: DDR1 WT or KO E0771 cells were firstly inoculated into Rag1-/- mice. When tumor volume reached approximately 200~300 mm3 (usually 20 days after inoculation), 60 mg of tumor organoid were transplanted to WT C57BL/6 mice. Tumor samples were collected on day 4 after transplantation for RNA-seq. Antibody treatment samples: DDR1 KO E0771 cells were reconstituted with human DDR1, then injected into C57BL/6 mice. Isotype control IgG or anti-hDDR1 ECD antibody treatment (10mg/kg intrutumural) started when tumor volume reached approximately 100 mm3. Tumor samples were collected on day 6 after treatment for RNA-seq. Results: Approximately 50 million sequence reads were obtained per sample and identified more than 20,000 transcript isoforms. Conclusions: The RNA-seq results represents the detailed analysis of DDR1 WT/KO mammary tumor transcriptomes in immunocompetent mice C57BL/6.
2021-09-07 | GSE139239 | GEO
Project description:Mice with mitochondrial complex I deficiency (Ndufs4-/-) suffer from severe energy impairment primarily affecting the brain and die at P55. A small molecule screen developed by our lab using cells harboring human mitochondrial disease mutations identified antibiotics targeting mitochondrial translation as potent inhibitors of cell death under nutrient stress conditions. Doxycycline, which was identified amongst these antibiotics, was administered in the diet of Ndufs4-/- mice after weaning at P21. Mice fed with doxycycline showed improved motor function and significantly increased lifespan relative to untreated Ndufs4-/- mice. In order to investigate the molecular changes promoted by doxycycline in the brains of these mice, Ndufs4-/- doxycycline treated (DOX), Ndufs4-/- untreated (KO), and Ndufs4+/+ (WT) control mice were sacrificed at P55 and their brains harvested. Proteomic analysis revealed doxycycline treatment largely prevented the neuroimmune and inflammatory profile identified in the Ndufs4-/- mice. These findings implicate a potentially causality of these proteins in the neuronal cell death ultimately leading to the observed brain pathology.
2021-09-09 | PXD022860 | Pride
Project description:To assess the role of LSD1 in mice small intestinal epithelium, small intestinal organoids were treated with an inhibitor for LSD1 (GSK-LSD1) and compared to untreated organoids. Similar to intestinal epithelium from mice with an intestinal epithelium specific LSD1-KO, paneth cells dissappear upon GSK-LSD1 treatment. We used these sequencing data to show that these small intestinal organoids have a similar phenotype as mice epithelium without LSD1.
2020-11-16 | E-MTAB-9077 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal of human cancers underscoring the need to identify new therapeutic vulnerabilities. Previously, we reported high expression of transcriptional co-regulators C-terminal binding proteins (CtBP) 1 and 2 in human PDAC, however their precise role in PDAC formation or progression remains unclear. Here, we have studied PDAC tumor dependency on CtBPs for growth and metastasis using an orthotopic syngeneic pancreatic tumor mouse model. CRISPR-based homozygous deletion of Ctbp2 dramatically decreased PDAC tumor growth, drastically reduced metastatic potential, and significantly prolonged survival. Interrogating differential gene expression of the orthotopic PDAC tumors from CtBP2 WT vs. CtBP2 KO cohorts, we identified significant downregulation of the EGFR-superfamily receptor ErbB3 in CtBP2 KO tumors, and further determined that CtBP regulates expression of both the ErbB2 and 3 EGFR superfamily genes in PDAC cells. We therefore hypothesized that CtBP regulation of physiologic ErbB2/3 signaling contributes, in part, to PDAC growth and metastasis. Indeed, we observed that CtBP2 KO cells exhibited severely attenuated activation of phospho-Akt after neuregulin stimulation of ErbB2/3, and we demonstrate that human PDAC cells also show CtBP dependence of ErbB2/3 expression. Our results suggest that a subset of PDAC tumors is dependent on physiologic ErbB2/3 signaling and could be targeted by pharmacologic inhibitors of ErbB2 and/or ErbB3. Providing proof of concept, the ErbB2-targeted multikinase inhibitor lapatinib, but not the ErbB1/EGFR targeted agent erlotinib, effectively killed ErbB3 expressing PDAC cells, while CtBP2 KO cells where ErbB3 expression was extinguished, were resistant to lapatinib. Taken together, our data suggests that ErBb2/3 targeted therapeutics can effectively target a critical PDAC dependency on physiologic ErbB2/3 signaling which is the result of CtBP’s oncogenic transcriptional program that drives PDAC tumor progression.
2023-11-10 | GSE228625 | GEO