C2C12 cells are mouse skeletal muscle cells. These cells were transfected with shRNA against FoxO1, FoxO3, and FoxO4. FoxO1, FoxO3, and FoxO4 are the known paralogues expressed in this cell line.
Codependent activators direct myoblast-specific MyoD transcription.
No sample metadata fields
View SamplesChromosomal instability (CIN) is defined by the propensity to acquire structural and/or numerical aberration in the normal cellular karyotype and is often associated with cancer. Autophagy is a catabolic process that leads to the recycling of cellular components that may positively or negatively impact on cancer development and progression, depending on the context. Recent work postulated that the depletion of the pro-autophagic and tumor suppressive protein Beclin 1 triggers CIN by interfering with mitotic chromosome segregation, providing a possible mechanism for how Beclin 1 can act as a tumor suppressor (Fremont et al., PMID: 23478334). Here, we present data supporting the notion that the phenotypes described in Fremont et al., depend on a siRNA off-target effect. The transcriptomic analysis shown here was designed to identify the factor(s) that are responsible for such phenotype.
Beclin 1 is dispensable for chromosome congression and proper outer kinetochore assembly.
Cell line
View SamplesDeregulation of cytokine- and growth factor signaling due to altered expression of endogenous regulators is well recognized in prostate and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of growth hormone, IGF and prolactin signaling, that have been implicated in carcinogenesis. In this study we elucidate expression pattern and functional significance of SOCS2 in prostate cancer (PCa). Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed significantly enhanced expression in tumor compared to benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited prostate cancer cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we prove for the first time that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with androgen receptor expression in malignant tissue of patients. Taken together, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo.
SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
Treatment, Time
View SamplesA non-functional myosin Vb motor in duodenal enterocytes results in disruption of epithelial cell polarity characterized by complete loss of microvilli and mislocalization of apical brush border proteins in the cytoplasm which finally cause a devastating disease in neonates with severe malabsorption defects accompanied by protracted diarrhea during infancy, classified as microvillus inclusion disease (MVID). The exact mechanisms how loss-of-function of MYO5B induces polarity loss are not completely understood in MVID pathogenesis. Obtaining better insights in cell polarity defects caused by loss of MYO5B, we performed microarray- in combination with protein expression-analysis in an inducible CaCo2 MYO5B RNAi cell system. Surprisingly, in MYO5B-depleted CaCo2 cells, CDH1 coding for the cell adhesion protein E-Cadherin and important for cell adhesion and therefore maintenance of cell polarity, was significantly downregulated. Interestingly, mesenchymal cell markers, specifically Vimentin and N-Cadherin, physiologically not expressed in differentiated epithelium, were upregulated and accompanied by increased phospho-c-jun levels in the nucleus. Importantly phospho-c-jun was also found in nuclei of duodenal enterocytes in MVID patients, indicating loss of MYO5B induces epithelial cell scattering in enterocytes.
Microvillus inclusion disease: loss of Myosin vb disrupts intracellular traffic and cell polarity.
Specimen part, Cell line
View SamplesThe subunits of voltage-gated calcium channels regulate surface expression and gating of CaV1 and CaV2 1 subunits, and thus contribute to neuronal excitability, neurotransmitter release and calcium-induced gene regulation. In addition certain subunits are targeted into the nucleus, where they directly interact with the epigenetic machinery. Whereas their involvement in this multitude of functions is reflected by a great molecular heterogeneity of isoforms derived from four genes and abundant alternative splicing, little is known about the roles of individual variants in specific neuronal functions. In the present study, an alternatively spliced 4 subunit lacking the variable N-terminus (4e) is identified. It is highly expressed in mouse cerebellum and cultured cerebellar granule cells (CGC) and modulates P/Q-type calcium currents in tsA cells and CaV2.1 surface expression in neurons. Compared to the other two known full-length 4 variants (4a, 4b) 4e is most abundantly expressed in the distal axon, but lacks nuclear targeting properties. To examine the importance of nuclear targeting of 4 subunits for transcriptional regulation, we performed whole genome expression profiling of CGCs from lethargic mice individually reconstituted with 4a, 4b, and 4e. Notably, the number of genes regulated by each 4 splice variant correlated with the rank order of their nuclear targeting properties (4b> 4a> 4e). Together these findings support isoform-specific functions of 4 splice variant in neurons, with 4b playing a dual role in channel modulation and gene regulation, while the newly detected 4e variant serves exclusively in calcium channel-dependent functions.
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
Specimen part
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesThe eukaryotic translation initiation factor (eIF) 3a is described in various tumor entities as potential tumor marker involved in development and progression of cancer. eIF3a is the largest subunit of the eIF3 complex, a key functional entity in 80S establishment and translation initiation. We hypothesize that eIF3a is more a specific than global translation initiator and involved in signalling pathways that are frequently targeted in UBC therapy.
eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of translation initiation.
Specimen part, Cell line, Treatment
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesIntroduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health
Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: A randomised double-blind, placebo-controlled, crossover trial.
Treatment, Subject
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