Inflammation has a causal role in many cancers. In prostate cancers, epidemiological data suggest a link between prostatitis and subsequent cancer development, but a proof for this concept in a tumor model has been lacking. A constitutively active version of the IkappaB kinase 2 (IKK2), the molecule activated by a plethora of inflammatory stimuli, was expressed specifically in the prostate epithelium. Signaling of the IKK2/NF-kappaB axis was insufficient for transformation of prostate tissue. However, while PTEN+/- epithelia exhibited intraepithelial neoplasias only recognizable by nuclear alterations, additional IKK2 activation led to an increase in tumor size and formation of cribriform structures and to a fiber increase in the fibroblastic stroma. This phenotype was coupled with inflammation in the prostate gland characterized by infiltration of granulocytes and macrophages. Molecular characterization of the tissues showed a specific loss of smooth muscle markers as well as expression of chemokines attracting immune cells. Isolation of epithelial and stromal cells showed differential chemokine expression by these cells. Correlation studies showed the inflammatory phenotype coupled to loss of smooth muscle in infiltrated glands, but maintenance of the phenotype in glands where inflammation had decreased. Despite the loss of the smooth muscle barrier, tumors were not invasive in a stable genetic background. Data mining revealed that smooth muscle markers are downregulated in human prostate cancers and literature data show that loss of these markers in primary tumors is associated with subsequent metastasis. Our data show that loss of smooth muscle and invasiveness of the tumor are not coupled. Thus, inflammation during early steps of tumorigenesis can lead to increased tumor size and a potential change in the subsequent metastatic potential, but the tumor requires an additional transformation to become a carcinoma.
Persistent inflammation leads to proliferative neoplasia and loss of smooth muscle cells in a prostate tumor model.
Age, Specimen part
View SamplesWe expressed a constitutively active mutant of MEK5 (MEK5D) in human primary endothelial cells (EC) to study the transcriptional and functional responses to Erk5 activation under static conditions.
Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4).
Cell line
View SamplesThe objective of this study was to compare the transcriptional repertoire of mature human neutrophils before and after GM-CSF treatment by using oligonucleotide microarrays.
RhoH/TTF negatively regulates leukotriene production in neutrophils.
Specimen part
View SamplesBackground: Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of stage M patients present with disseminated tumor cells (DTCs) in the bone marrow (BM). Although these cells represent a major obstacle in the treatment of neuroblastoma patients, their transcriptomic profile was not intensively analyzed so far. Results: RNA-Seq of stage M primary tumors, enriched BM-derived DTCs and the corresponding non-tumor mononuclear cells (MNCs) revealed that DTCs largely retained the gene expression signature of tumors. However, we identified 322 genes that were differentially expressed (q < 0.001, |log2FC|>2). Particularly genes encoded by mitochondrial DNA were highly up-regulated in DTCs, whereas e.g. genes involved in angiogenesis were down-regulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8x10-75 log2FC > 6). Interestingly, we found that the gene expression profiles of diagnostic DTCs largely resembled those of relapse DTCs with only 113 differentially expressed genes under relaxed cut-offs (q < 0.01, |log2FC| > 0.5). Notably, relapse DTCs showed a positional enrichment of 31 down-regulated genes encoded by chromosome 19, including five tumor suppressor genes (SIRT6, PUMA, STK11, CADM4 and GLTSCR2). Conclusion: This first RNA-Seq analysis of DTCs from neuroblastoma patients revealed their unique expression profile in comparison to the corresponding MNCs and tumor samples, and, interestingly, also expression differences between diagnostic and relapse DTCs preferentially affecting chromosome 19. As these alterations might be associated with treatment failure and disease relapse, they should be considered for further functional studies. Overall design: Tumor (n=16), bone marrow-derived disseminated tumor cells (n=42) and corresponding bone marrow-derived non-tumor cells (n=28) of stage M neuroblastoma patients were used for RNA-Seq
Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression.
Specimen part, Subject
View SamplesWe aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex.
Specimen part, Cell line
View SamplesDuring development, thymocytes bearing a moderately self-reactive T cell receptor (TCR) can be selected to become regulatory T (Treg) cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined.
Continuous T cell receptor signals maintain a functional regulatory T cell pool.
Specimen part
View SamplesDuring kidney development segmented epithelia of the nephron derive from progenitor cells in the metanephric mesenchyme after induction by secreted molecules from the ureteric bud. We have identified three distinct inductive activities from a ureteric bud cell line. These include leukemia inhibitory factor (LIF), neutrophil gelatinase-associated lipocalin (NGAL) and an active fraction currently referred to as ANX. Each of these activities induces segmented nephron epithelia in isolated rat metanephric mesenchyme over a time period of 7 days. This study was designed to characterize the temporal sequence of gene expression in the course of the conversion process induced by each of the distinct inducers.
beta-catenin/TCF/Lef controls a differentiation-associated transcriptional program in renal epithelial progenitors.
Time
View SamplesWe investigated the ability of transferrin receptor1 (TfRc) knockout cells to populate different domains of the developing kidney by using a chimeric approach. The TfRc cells developed into all segments of the developing nephron, but there was a relative exclusion from the ureteric bud and a positive bias towards the stromal compartment. Here we conducted a microarray analysis of differential gene expression between TfRc deficient and wild type (wt) cells in chimeric embryonic kidneys derived from embryos created by blastocyst injection of wt blastocysts with TfRc-/- green fluorescent protein-expressing (GFP+) embryonic stem cells.
Scara5 is a ferritin receptor mediating non-transferrin iron delivery.
No sample metadata fields
View SamplesCsUBC13 was identified via proteomics from iron starvation treated Cucumber root. ubc13A is an ABRC seed stock (CS51269). CS851269 was purchased from ABRC and confirmed as homozygous Atubc13A knock-out T-DNA mutant. We generated transgenic arabidopsis with ectopic expression of CsUBC13 gene under control of the cauliflower 35S promotor. Both genotypes and Col-0 were used to investigate the transcriptional response to Iron (Fe) deficiency.
A lysine-63-linked ubiquitin chain-forming conjugase, UBC13, promotes the developmental responses to iron deficiency in Arabidopsis roots.
Specimen part
View SamplesWe have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis.
Expression of constitutively active FoxO3 in murine forebrain leads to a loss of neural progenitors.
Specimen part
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