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 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 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 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Specimen part, Cell line
View SamplesSorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Specimen part, Cell line
View SamplesSorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Specimen part, Cell line
View Samples