We 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 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 SamplesInflammation 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 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 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 Samples3 samples, 2 reps each. comparison of wildtype cotyledon to RNAioleosin transgenic
Suppression of soybean oleosin produces micro-oil bodies that aggregate into oil body/ER complexes.
No sample metadata fields
View SamplesSmac mimetics are considered as promising cancer therapeutics, but little is yet known about how they alter gene expression. In this study we used an unbiased genome-wide expression array to investigate Smac mimetic BV6-induced gene regulation in breast cancer cell lines. Kinetic analysis revealed that BV6 alters gene expression in two waves. The first wave primarily involves NF-B- and AP-1 families of transcription factors, while the second wave largely depends on tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, disrupting auto-/paracrine tumor necrosis factor- (TNF)/ (TNFR1) signaling by knockdown of TNFR1 strongly attenuates the BV6-induced second wave of gene expression and upregulation of many pathways including NF-B signaling, apoptosis and immune signalling, but not MAPK signaling pathways. Consistently, BV6 stimulates phosphorylation of cJun, a marker of MAPK cascade activation, irrespective of the presence or absence of the TNF blocking antibody Enbrel. We show here in a comprehensive overview that BV6-induced gene expression in breast cancer cells takes place in a time- as well as TNFR1-dependent manner.
Smac mimetic induces an early wave of gene expression via NF-κB and AP-1 and a second wave via TNFR1 signaling.
Cell line, Treatment
View SamplesThe pituitary gland is a neuroendocrine organ that is involved in several processes within the body such as metabolism, growth, immune function, and reproduction. Increased ambient temperatures are environmental stressor that leads to several welfare concerns in poultry production but also economic losses. Because of the involvement of the pituitary gland in several processes that are affected by heat stress, it is hypothesized this tissue''s gene expression will be impacted by heat stress. The objectives of the project are to (a) identify genes that constitue the pituitary gland when compared to other collected chicken tissues (Insert tissues) and (b) identify genes that respond to heat stress via differential expression analysis to better understand the chicken''s response to heat at the transcriptomic level. Overall design: Ross 708 broiler chickens were raised from day of hatch to day 42, typical market age, on the University of Delaware farm. Birds were placed into two separate houses, one thermoneutral house and one experimental (heat stress) house. Both houses were kept at 23 hours of light and 1 hour of dark and birds were placed on litter and given feed (meeting all NRC requirements) and water with ad libitum access. Both houses were kept at 35 degrees celsius for the first week and the temperature was decreased 5 degrees celsius each week until 25 degrees celsius. The thermoneutral hosue was maintained at 25 degrees celsius for the remainder of the study. Starting on day 21, the experimental house began a cyclical heat stress scheme with 8 hours per day of increased temperatures (35 - 37 degrees celsius) through completion of the trial at day 42. Necropsies were performed at several points throughout the trial (days 21, 22, 26, 32, and 42).
Transcriptomic changes throughout post-hatch development in Gallus gallus pituitary.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tailoring high-density oligonucleotide arrays for transcript profiling of different Arabidopsis thaliana accessions using a sequence-based approach.
Specimen part
View SamplesDue to limited bio-availability of Fe, plants evolved adaptive alterations in development regulated at the transcriptional level. We investigated the early transcriptional response to Fe deficiency.
Early iron-deficiency-induced transcriptional changes in Arabidopsis roots as revealed by microarray analyses.
Specimen part
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