This SuperSeries is composed of the SubSeries listed below.
Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.
Specimen part, Treatment
View SamplesIn this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated -gal (SA--gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, Focal adhesion kinase and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies which rely on senescence induction by inhibiting Shp2 or controlling its target gene products may be useful in blocking breast cancer.
Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.
Specimen part, Treatment
View SamplesIn this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated -gal (SA--gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, Focal adhesion kinase and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies which rely on senescence induction by inhibiting Shp2 or controlling its target gene products may be useful in blocking breast cancer.
Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.
Specimen part, Treatment
View SamplesAnalysis of genes regulated by Maf and donwstream of ErbB2 in P8 Schwann cells
Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells.
Specimen part
View SamplesThe zinc finger factor Insm1 is known to regulate differentiation of pancreatic cells during development, Here we show that Insm1 is essential for the maintenance of functionally mature pancreatic cells in mice.
Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function.
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View SamplesThe combined activation of Wnt/-catenin and MET/HGF is required for mammary cancer stem cell (MaCSC) maintenance. We generated mammospheres derived from tumors of mice harboring Wnt/Met signaling mutations on which we performed microarray analysis to evaluate gene expression signatures controlled by Wnt and MET pathways. We used the gene expression profiles to dissect the role and the functions of these pathways in MaCSCs.
Combined Wnt/β-catenin, Met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome.
Specimen part, Treatment
View SamplesWe explored the connection between C/EBPa (CCAAT/enhancer binding protein a) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPa was expressed in human and murine intestinal epithelia in the transit amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APCMin/+ polyps, C/EBPa was absent from nuclear ß-catenin–positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPa KO in murine gut epithelia increased tumor volume. C/EBPa deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of ß-catenin in organoids attenuated C/EBPa expression. Comparing gene expression of wild type and C/EBPa KO organoids by RNA sequencing aimed to identify C/EBPa dependent alterations in gene expression. Overall design: These data suggest homeostatic and oncogenic suppressor functions of C/EBPa in the gut by restricting Wnt signaling.
A C/EBPα-Wnt connection in gut homeostasis and carcinogenesis.
Specimen part, Subject
View SamplesWe have noticed that the proliferative potential of epithelial cells in the mouse proximal prostatic ducts is less than those at the distal prostatic ducts. To determine whether specific signaling is differentially activated in distal and proximal prostate basal cells, we isolated respective basal cells in the two regions and performed an RNA-seq analysis. Overall design: Two group comparison
Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.
Specimen part, Cell line, Subject
View SamplesTo identify such inhibitory signaling mediated by the stromal cells with active Wnt activity, we performed an RNA-seq analysis comparing the gene expression profiles of primarily cultured adult mouse prostate stromal cells that express S37A ß-Catenin and the control cells that only express GFP. We identified 783 genes that were differentially expressed by at least 1.2 fold (Fig. 4A). Genes associated with the Wnt receptor signaling pathway were enriched in the S37A ß-catenin group, corroborating the higher Wnt activity in this group. Overall design: Two group comparison
Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.
Cell line, Subject
View SamplesComapare the global expression of metafemales and normal femalems Overall design: Collected the metafemales, females and males and made RNA-seq
Dosage compensation and inverse effects in triple X metafemales of Drosophila.
Sex, Subject
View Samples