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Gene expression profiling of Stat3flx/flx/NIC breast tumors compared to wild type NIC tumors.

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)

ORGANISM(S): Mus musculus

PROVIDER: GSE15632 | GEO | 2009/09/01

SECONDARY ACCESSION(S): PRJNA115629

REPOSITORIES: GEO

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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.

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Gene expression profiling of Stat3flx/flx/NIC breast tumors compared to wild type NIC tumors.

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