In this study we could show that the treatment of primary murine prostate cancer(PCa) cells derived from the well-established TRAMP (transgenic adenocarcinoma ofmouse prostate) model with the histone deacetylase inhibitor (HDI) valproic acid (VPA) has an anti-proliferative, anti-migrative and anti-invasive effect on the cells.To our knowledge this is the first study that identified that treatment of PCa cells with VPA leads to the re-expression of cyclin D2, which is known to be frequently inactive in patients with PCa. Additionally, we could demonstrate that VPA specifically induces re-expression of cyclin D2 as a family member of the highly conserved Dtype cyclins in human colorectal and mammary gland adenocarcinoma cell lines, whereas VPA treatment has no effect in NIH/3T3 fibroblasts. The observed cyclin D2 re-expression in cancer cells is activated by an increase of histone acetylation in the promoter region of the cyclin D2 gene and might be the underlying molecular mechanism of the inhibition of proliferation of cancer cells after VPA treatment. Taken together, our results confirm VPA as an anticancer therapeutic option in tumors with epigenetically repressed cyclin D2 expression.
Valproic acid inhibits the proliferation of cancer cells by re-expressing cyclin D2.
Specimen part
View SamplesAffymetrix exon array data were generated from total RNA that was isolated from localized Ewing sarcoma biopsy specimens. Expression of transcript summarized data was compared to data generated from normal stem cells and normal adult tissues.
Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.
Specimen part
View SamplesExpression profiles were generated from hESC-derived neural crest stem cells following transduction with GFP control vector or EWS-FLI1 vector. Expression was analyzed in stem cell conditions 5 days after transduction (undifferentiated conditions) and after 6 weeks in differentiation media (differentiation conditions).
Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.
Specimen part, Treatment
View SamplesThe chromatin of individual chromosomes is organized into chromosome territories (CTs) in the interphase nucleus. The spatial arrangement of CTs is non-random and evolutionarily conserved. The gene-dense and gene-poor CTs are positioned in the nuclear center and periphery, respectively. As candidates for key molecules involved in nuclear organization, we have investigated the nuclear actin-related proteins (Arps), which include the evolutionarily conserved actin-family together with conventional actin. We used a conditional knockout system with chicken DT40 cells to analyze the functions of the actin-related protein Arp6. Consistent with a previous identification of Arp6 in the SRCAP chromatin remodeling complex, the histone variant H2AZ was significantly decreased in the chromatin of Arp6-deficient cells. Most importantly, Arp6-deficient cells had impaired radial positioning of both gene-poor macrochromosome and gene-rich microchromosome CTs. A transcription microarray analysis of the cells suggests that the radial positioning of CTs impacts only a limited number of genes and plays an active role in repression, rather than in induction. As far as we know, this report is the first observation that an inner nuclear protein is required for the radial distribution of CTs, and will provide new insight into the mechanisms and physical significance of the positioning of CTs in the nucleus.
The actin family member Arp6 and the histone variant H2A.Z are required for spatial positioning of chromatin in chicken cell nuclei.
No sample metadata fields
View SamplesThe histone variant H2A.Z is evolutionarily conserved from yeast to vertebrates. H2A.Z regulates gene expression when localized to promoter region. Recently, we identified two genes encoding H2A.Z, H2A.Z-1 and H2A.Z-2 in vertebrate genome. However, it is not clear that both H2A.Z-1 and H2A.Z-2 were required for the function of H2A.Z in gene regulation. To address this issue, we generated the H2A.Z-1 and H2A.Z-2 double knock out (KO) cells in chicken DT40 cells. The expression pattern of H2A.Z-1 and H2A.Z-2 double KO cells was compared with WT cells to characterize the genes regulated by H2A.Z-1 and H2A.Z-2.
The actin family member Arp6 and the histone variant H2A.Z are required for spatial positioning of chromatin in chicken cell nuclei.
Specimen part, Cell line
View SamplesNull mutations in the SAL1 protein, a bi-functional protein with inositol polyphosphate-1-phosphotase activity and nucleosidase activity, result in mutants with altered leaf morphology, delayed growth and tolerance to drought stress. This experiment examines the gene expression of two SAL1 mutants, alx8 in the Col-0 background and fry1-1 in the C24 background, under normal growth conditions. In brief, RNA was extracted from the leaves of three plants of each mutant and their respective ecotypes two hours after lights on. Plants were grown under normal conditions for 5 weeks before harvesting. Each array represent a single biological replicate.
The nucleotidase/phosphatase SAL1 is a negative regulator of drought tolerance in Arabidopsis.
Age, Specimen part
View SamplesObjective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range.
Liver adapts mitochondrial function to insulin resistant and diabetic states in mice.
Sex, Specimen part, Treatment
View SamplesMost autoreactive B cells are normally counterselected during early B cell development. To determine whether Toll-like receptors (TLRs) regulate the removal of autoreactive B lymphocytes, we tested the reactivity of recombinant antibodies from single B cells isolated from patients deficient for IL-1R-associated kinase (IRAK)-4, myeloid differentiation factor 88 (MyD88) and UNC-93B. Indeed, all TLRs except TLR3 require IRAK-4 and MyD88 to signal and UNC-93B-deficient cells are unresponsive to TLR3, TLR7, TLR8 and TLR9. All patients suffered from defective central and peripheral B cell tolerance checkpoints resulting in the accumulation of large numbers of autoreactive mature nave B cells in their blood. Hence, TLR7, TLR8, and TLR9 may prevent the recruitment of developing autoreactive B cells in healthy donors. Paradoxically, IRAK-4-, MyD88- and UNC-93B-deficient patients did not display autoreactive antibodies in their serum nor developed autoimmune diseases, suggesting that IRAK-4, MyD88 and UNC-93B pathway blockade may thwart autoimmunity in humans.
IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Endothelial GATA4 controls liver fibrosis and regeneration by preventing a pathogenic switch in angiocrine signaling.
Specimen part, Treatment
View SamplesLiver sinusoidal endothelial cells (LSEC) constitute discontinuous, permeable microvessels, with a characteristic program of gene expression that differs significantly from continuous microvascular endothelial cells e.g. in the lung. Gata4 is described as master regulator of LSEC specification during liver development. Here, we sought to analyze the role of endothelial Gata4 in the adult liver.
Endothelial GATA4 controls liver fibrosis and regeneration by preventing a pathogenic switch in angiocrine signaling.
Specimen part
View Samples