Gene expression profiling of Stat3flx/flx/NIC breast tumors compared to wild type NIC tumors.
Ontology highlight
ABSTRACT: A Stat3-dependent transcription regulatory network involved in inflammation and metastasis is identified. Analyses of the gene expression data revealed that Stat3flx/flx/NIC tumors exhibited a significant reduction in the expression of factors involved in both tumor angiogenesis (fibronectin, von willebrand factor, annexin a3, thrombopoietin, fibulin 5) and in the acute phase inflammatory response (cebpd, osmr, saa1, saa2)
Project description:A Stat3-dependent transcription regulatory network involved in inflammation and metastasis is identified. Analyses of the gene expression data revealed that Stat3flx/flx/NIC tumors exhibited a significant reduction in the expression of factors involved in both tumor angiogenesis (fibronectin, von willebrand factor, annexin a3, thrombopoietin, fibulin 5) and in the acute phase inflammatory response (cebpd, osmr, saa1, saa2) Experiment Overall Design: Common reference design. 8 samples including RNA extracted from 3 pools of Stat3wt/wt/NIC (WT) tumor tissues (5 individual tumor samples per pool) and 5 individual Stat3flx/flx/NIC (Homo) tumor tissue samples.
Project description:Mammary tumors of parental and aggressive variants of an ErbB2+ breast cancer mouse model that differs in the degree to which is is experiencing oxidative stress as a result of forced expression of an oxidative stress inducer called p66ShcA.
Project description:Using proteomics and complexome profiling we studied longitudinal variations in the plasma proteome of two kidney transplant recipients, prior to and after their transplantation, in comparison to two healthy controls. Their post-transplant course was complicated with several bacterial infections, resulting in dramatic changes in the plasma proteome, especially in acute phase protein concentrations. As positive acute phase proteins, being elevated upon inflammation, we observed the well-known C-reactive protein (CRP) and Serum Amyloid A (SAA1 and SAA2), but also Fibrinogen (FGA, FGB and FGG), Haptoglobin (HP), Leucine-rich alpha-2-glycoprotein (LRG1), Lipopolysaccharide-binding protein (LBP), Alpha-1-antitrypsin (SERPINA1), Alpha-1-antichymotrypsin (SERPINA3), Protein S100 (S100A8, S100A9), Complement protein C4, C4b-binding protein alpha chain (C4BPA), Complement factor B (CFB) and Monocyte differentiation antigen CD14. As negative acute phase proteins, being downregulated upon inflammation, we identified the well-documented Serotransferrin (TF) and Transthyretin (TTR), but also Kallistatin (SERPINA4), Heparin cofactor 2 (SERPIND1), Inter-alpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For patient P2, who showed the most severe acute phase response, we additionally performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observe that several plasma proteins displaying alike concentration patterns, co-elute and possibly form macromolecular complexes. These include a) FGA, FGB and FGG (naturally, b) ITIH1 and ITIH2, c) HP and Hemoglobin (HB), d) the small acute phase biomarker proteins SAA1 and SAA2 with the Apolipoproteins A-I, A-II, A-IV (APOA1, APOA2, APOA4). By complexome profiling we expose how SAA1 and SAA2 likely become incorporated into high-density lipid particles, thereby replacing partly APOA1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on the correlated variations in the abundance of several plasma proteins upon inflammatory events.
Project description:CdGAP/ARHGAP31 is a molecular target of TGFb-mediated EMT and required for Her2-positive breast cancer growth and metastasis Metastasis is the leading cause of death in breast cancer patients. The epithelial-to-mesenchymal transition (EMT) has a crucial role in metastasis and is highly critical for tumor cell dissemination. CdGAP/ARHGAP31 is highly expressed in breast cancer tissues and is associated with poor clinical outcome in breast cancer patients. CdGAP cooperates in a GAP-independent manner with the transcriptional repressor Zeb2 to function as a critical modulator of breast cancer through repression of E-cadherin transcription. In this study, we used a murine model of Her2+ breast cancer to investigate further the role of CdGAP in breast tumorigenesis. We found that CdGAP was essential for tumor formation and metastasis to the lungs in the Her2+ mouse breast cancer model. We determined that CdGAP is required for intravasation and growth at the metastatic sites. By using global gene expression approaches, we found that CdGAP depletion in Her2+ primary tumors was associated with an EMT signature, including a decreased expression of the metastatic factor claudin-2 and an increase in E-cadherin expression. In Her2+ breast cancer cells, CdGAP expression is positively regulated by the TGFb canonical pathway in a smad-dependent manner and regulates cell proliferation, migration, invasion, and adhesion. CdGAP was found to interact with the focal adhesion protein Talin and regulates focal adhesion dynamics in breast cancer cells. Collectively, CdGAP appears as a potential anti-metastatic target for the treatment of Her2+ breast cancer.
Project description:To elucidate IL-17A-dependent immune mechanims involved in regulating host defense, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential of regulating protective immunity that failed to be upregulated in the absence of IL-17RA signaling. Whole small intestine tissue collected from IL-17RA-deficient and C57BL/6 (wild-type) mice was collected 2 weeks after Giardia muris infection and from uninfected controls. Expression levels of several genes that may have anti-parasitic potential (Defb1, Retnlb, Saa1, Saa2) and may be involved in parasite clearance were, on average, lower or unchanged in IL-17RA deficient compared to wild-type mice after infection.
Project description:To elucidate IL-17A-dependent immune mechanims involved in regulating host defense, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential of regulating protective immunity that failed to be upregulated in the absence of IL-17RA signaling. Whole small intestine tissue collected from IL-17RA-deficient and C57BL/6 (wild-type) mice was collected 2 weeks after Giardia muris infection and from uninfected controls. Expression levels of several genes that may have anti-parasitic potential (Defb1, Retnlb, Saa1, Saa2) and may be involved in parasite clearance were, on average, lower or unchanged in IL-17RA deficient compared to wild-type mice after infection. Two weeks after Giardia muris challenge, total RNA was extracted and analyzed from tissue of the small intestines of infected IL-17RA-deficient and wild-type mice, and compared to uninfected controls. Each sample contained equal amounts of total RNA from 6 female mice which were pooled and used in the experiment.