Analysis of Gene Expression in PTHrP-/- Mammary Buds Supports a Role for BMP Signaling and MMP2 in the Initiation of Ductal Morphogenesis.
Analysis of gene expression in PTHrP-/- mammary buds supports a role for BMP signaling and MMP2 in the initiation of ductal morphogenesis.
Specimen part
View SamplesCell migration contributes to normal development and homeostasis as well as to pathological processes such as inflammation and tumor metastasis. Previous genetic screens have revealed a few major signaling pathways that govern follicle cell migrations in the Drosophila ovary, several of which elicit transcriptional responses. However few downstream targets of the critical transcriptional regulators, such as the C/EBP homolog SLBO, have been identified. To characterize the gene expression profile of two migratory cell populations and identify SLBO targets, we employed a magnetic bead based cell separation approach to purify border cells and centripetal cells expressing the mouse CD8 antigen, and carried out whole genome microarray analysis.
Analysis of cell migration using whole-genome expression profiling of migratory cells in the Drosophila ovary.
Sex, Specimen part
View SamplesNotch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
View SamplesMicroarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Age, Specimen part
View SamplesA comparison of gene expression in the mammary gland of lactating mice at day 9 after parturition between Akt -/- and wildtype individuals.
Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation.
Sex, Age, Specimen part, Subject
View SamplesTo test whether SVD regression is sufficiently sensitive to detect activation of a secondary, endogenous pathway as it occurs following ectopic manipulation of a strong primary pathway by focusing on the relationship between the Ras and TGF signaling pathways.
Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo.
No sample metadata fields
View SamplesG1E cells are a Gata-1 erythroid-committed cell line derived from targeted disruption of Gata-1 in embryonic stem cells. The ER4 subclone contains an inducible form of Gata-1 (Gata-1-ER, Gata-1 fused to the estradiol receptor ligand binding domain). We performed transcriptome analysis using this cell line. Estradiol was added to culture medium triggering synchronous and homogenous differentiation. At various time points, RNA was sampled and analyzed using the Affymetrix MG-U74Av2 platform. Three biological replicas (A,B, and C) were performed. The thirty hour time course corresponds to development from the late BFU-E stage through the orthochromatic erythroblast stage.
Global regulation of erythroid gene expression by transcription factor GATA-1.
No sample metadata fields
View SamplesWe performed RNAseq on subpopulations of mammary epithelial cells. We carried out sorting of a gradient of s-SHIP positive cells in the mammary gland (neg, low, and hi for s-SHIP eGFP). High sSHIP-eGFP populations denote a postulated stem cell population, while low and negative represent more differentiated cell types. s-SHIP eGFP hi to negative potentially represents a gradient from stem to more differentiated progeny, respectively, within the basal epithelial compartment. We FACS sorted 3 replicates for each cell type to represent s-SHIP-neg, s-SHIP-low, and s-SHIP-high. Overall design: We FACS sorted 3 replicates for each cell type to represent s-SHIP-neg, s-SHIP-low, and s-SHIP-high, profiling each of these groups using RNA sequencing.
WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis.
Cell line, Subject
View SamplesNon-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. The oxygen-sensitive Hypoxia Inducible Factor (HIF) transcriptional regulators HIF-1 and HIF-2 are overexpressed in many human NSCLCs, and constitutive HIF-2 activity can promote murine lung tumor progression, suggesting that HIF proteins may be effective NSCLC therapeutic targets. To investigate the consequences of inhibiting HIF activity in lung cancers, we deleted Hif-1 or Hif-2 in an established KrasG12D-driven murine NSCLC model. Deletion of Hif-1 had no obvious effect on tumor growth, whereas Hif-2 deletion resulted in an unexpected increase in tumor burden that correlated with reduced expression of the candidate tumor suppressor gene Scgb3a1 (HIN-1).
HIF-2alpha deletion promotes Kras-driven lung tumor development.
No sample metadata fields
View SamplesWe previously identified a novel SNF1/AMPK-related protein kinase, Hunk, from a mammary tumor arising in an MMTV-neu transgenic mouse. The function of this kinase is unknown. Using targeted deletion in mice, we now demonstrate that Hunk is required for the metastasis of c-myc-induced mammary tumors, but is dispensable for normal development. Reconstitution experiments revealed that Hunk is sufficient to restore the metastatic potential of Hunk-deficient tumor cells, as well as defects in migration and invasion, and does so in a manner that requires its kinase activity. Consistent with a role for Hunk in the progression of human cancers, the human homologue of Hunk is overexpressed in aggressive subsets of carcinomas of the ovary, colon, and breast. In addition, a murine gene expression signature that distinguishes Hunk-wild type from Hunk-deficient mammary tumors predicts clinical outcome in women with breast cancer. Together, these findings establish a role for Hunk in metastasis and an in vivo function for this kinase.
The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis.
No sample metadata fields
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