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Facilitates chromatin transcription complex is a marker and target of aggressive cancers with lower survival rates

ABSTRACT: The Facilitates Chromatin Transcription (FACT) is involved in chromatin remodeling during transcription, replication and DNA repair and is considered to be an ubiquitously expressed complex that has no known associations with any disease. However, we discovered that FACT is expressed in very limited number of cells of adult mammalian organism, mostly presented by stem and undifferentiated cells. Here, we show that FACT is present in poorly differentiated aggressive cancers with an overall low survival rate. FACT acts as an "accelerator" of tumor transformation. It cannot drive transformation like an oncogene, but it increases the efficiency of oncogene-induced transformation. FACT expressing cancer cells cannot grow in the absence of FACT possibly due to the FACT involvement in selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation and that are induced in response to cell stress. We propose that FACT is a marker of an aggressive cancer phenotype and Patients with FACT-positive tumors are noted for an overall poorer survival rate. FACT expression in primary tumors may be used as a predictor of metastatic disease. FACT may also be used as a target of anti-cancer therapy because tumor cells expressing FACT are dependent on FACT function, while normal cells either do not express FACT or are not sensitive to FACT inhibition. Examination of AR binding sites of 3 replicates of untreated cells and 3 replicates of curaxin-treated cells, each with 3 replicate controls

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Leach

PROVIDER: E-GEOD-45393 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Facilitates chromatin transcription complex is a marker and target of aggressive cancers with lower survival rates

Project description:The Facilitates Chromatin Transcription (FACT) is involved in chromatin remodeling during transcription, replication and DNA repair and is considered to be an ubiquitously expressed complex that has no known associations with any disease. However, we discovered that FACT is expressed in very limited number of cells of adult mammalian organism, mostly presented by stem and undifferentiated cells. Here, we show that FACT is present in poorly differentiated aggressive cancers with an overall low survival rate. FACT acts as an "accelerator" of tumor transformation. It cannot drive transformation like an oncogene, but it increases the efficiency of oncogene-induced transformation. FACT expressing cancer cells cannot grow in the absence of FACT possibly due to the FACT involvement in selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation and that are induced in response to cell stress. We propose that FACT is a marker of an aggressive cancer phenotype and Patients with FACT-positive tumors are noted for an overall poorer survival rate. FACT expression in primary tumors may be used as a predictor of metastatic disease. FACT may also be used as a target of anti-cancer therapy because tumor cells expressing FACT are dependent on FACT function, while normal cells either do not express FACT or are not sensitive to FACT inhibition.

2013-03-22 | GSE45393 | GEO

Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization [Expression Array]

Project description:To determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng. Additional time points during transformation and activation were sequenced as well, but not assayed for expression. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed.

2013-09-17 | E-GEOD-49628 | biostudies-arrayexpress

Gene Expression in Human Lung Type II Cells

Project description:Normal lung function relies on mature function of alveolar type II cels, which have numerous functions including to regulate ion and fluid flux, produce immune molecules, and synthesize and secrete surfactant to stabilize air spaces. Differentiation of type II cells from precursor epithelial cells is accelerated by exposure of cultured cells to glucocorticoid and cAMP. In these studies we used DNA microarray analysis to identify genes of both fetal and adult type II cells that are regulated by glucocorticoid plus cAMP. In the first series of experiments we isolated epithelial cells from fetal human lung and cultured cells for 5 days with or without hormone treatment (dexamethasone plus 8-Br-cAMP plus isobutylmethylxanthine, DCI) and then performed DNA microarray analysis. In the second series of experiments, we isolated type II cells from adult human postmortem lung and cultured cells for 5 days with or without DCI and performed DNA microarray analysis.

2009-12-30 | E-GEOD-19699 | biostudies-arrayexpress

Rhesus macaque ileal loop study

Project description:Salmonella enterica serotype Typhimurium cause a localized enteric infection in immunocompetent patients while human immunodeficiency virus (HIV)-infected patients develop a life threatening bacteremia. We used a rhesus macaque ileal loop model to study how simian immunodeficiency virus (SIV) infection triggers defects in mucosal barrier function that enhance S. Typhimurium dissemination. SIV infection resulted in significant depletion of CD4+ T cells in the intestinal mucosa. Gene expression profiling revealed a defective TH17 response (with suppression of IL-17 and IL-22 expression) and impaired homeostasis of the intestinal epithelium in SIV-infected animals during NTS infection. These findings correlated with an impaired ability of lamina propria CD4+ T cells from SIV-infected macaques to produce IL-17 upon ex vivo stimulation, while production of IFNï§ was not affected. This cytokine imbalance in SIV-infected animals was associated with reduced expression of genes required for intestinal epithelial maintenance and repair, increased fluid secretion during NTS infection, epithelial damage and translocation of a non-invasive S. Typhimurium mutant. Although no defects in neutrophil recruitment were noted, the ileum of SIV-infected animals contained lower levels of the enzyme myeloperoxidase, which may indicate defects in neutrophil killing capacity. S. Typhimurium was recovered in markedly increased numbers from the mesenteric lymph nodes of SIV-infected macaques, illustrating the increased potential for systemic dissemination during co-infection. Our data suggest that SIV-infection causes a multi-factorial defect in mucosal barrier function that promotes bacterial dissemination. Keywords: Disease state analysis Comparison of ileal gene expression profiles in SIV infected rhesus macaques in response to Salmonella challange.

2010-05-26 | E-GEOD-10567 | biostudies-arrayexpress

Transcription profiling by array of mouse immortalized embryonic fibroblasts to identify genes regulated by mTORC1

Project description:Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a M-^Slow/low/high/lowM-^T or M-^SLLHLM-^T, which allowed the identification of genes regulated by mTORC1 by performing the appropriate comparisons

2011-08-02 | E-GEOD-27982 | biostudies-arrayexpress

The functional potential of high Arctic permafrost

Project description:The fate of the carbon stocked in permafrost soils following global warming and permafrost thaw is of major concern in view of the potential for increased CH4 and CO2 emissions from these soils. Complex carbon compound degradation and greenhouse gas emissions are due to soil microbial communities, but their composition and functional potential in permafrost soils are largely unknown. Here, a 2 m deep permafrost and its overlying active layer soil were subjected to metagenome sequencing, quantitative PCR, and microarray analyses. The active layer soil and 2 m permafrost soil microbial community structures were very similar, with Actinobacteria being the dominant phylum. The two soils also possessed a highly similar spectrum of functional genes, especially when compared to other already published metagenomes. Key genes related to methane generation, methane oxidation and organic matter degradation were highly diverse for both soils in the metagenomic libraries and some (e.g. pmoA) showed relatively high abundance in qPCR assays. Genes related to nitrogen fixation and ammonia oxidation, which could have important roles following climatic change in these nitrogen-limited environments, showed low diversity but high abundance. The 2 m permafrost soil showed lower abundance and diversity for all the assessed genes and taxa. Experimental biases were also evaluated and showed that the whole community genome amplification technique used caused large representational biases in the metagenomic libraries. This study described for the first time the detailed functional potential of permafrost-affected soils and detected several genes and microorganisms that could have crucial importance following permafrost thaw. A 2m deep permafrost sample and it overlying active layer were sampled and their metagenome analysed. For microarray analyses, 8 other soil samples from the same region were used for comparison purposes.

2010-05-06 | E-GEOD-20073 | biostudies-arrayexpress

Differences in major bacterial taxa in three high Arctic soils lead to different CO2 production rates

Project description:The melting of permafrost and its potential impact on greenhouse gas emissions is a major concern in the context of global warming. The fate of the carbon trapped in permafrost will largely depend on soil physico-chemical characteristics, among which are the quality and quantity of organic matter, pH and water content, and on microbial community composition. In this study, we used microarrays and real-time PCR (qPCR) targeting 16S rRNA genes to characterize the bacterial communities in three different soil types representative of various Arctic settings. The microbiological data were linked to soil physico-chemical characteristics and CO2 production rates. Microarray results indicated that soil characteristics, and especially the soil pH, were important parameters in structuring the bacterial communities at the genera/species levels. Shifts in community structure were also visible at the phyla/class levels, with the soil CO2 production rate being positively correlated to the relative abundance of the Alphaproteobacteria, Bacteroidetes, and Betaproteobacteria. These results indicate that CO2 production in Arctic soils does not only depend on the environmental conditions, but also on the presence of specific groups of bacteria that have the capacity to actively degrade soil carbon. Three different soil types from the Canadian high Arctic were sampled at two depths within the active layer of soil and at two sampling dates (winter and summer conditions), for a total of 20 samples.

2011-01-01 | E-GEOD-24800 | biostudies-arrayexpress

Cell-type specific transcriptome analysis to study germline development and reproduction in apomictic Boechera gunnisoniana- ATH1 arrays

Project description:Apomixis differs from sexual reproduction only in three major aspects: While the sexual megaspore mother cell undergoes meiosis, the apomictic initial cell omits or aborts meiosis (apomeiosis); the unreduced egg cell of apomicts forms an embryo without fertilization (parthenogenesis), and formation of functional endosperm requires specific developmental adaptations. Currently, our knowledge about the gene regulatory programs underlying apomixis is scarce. We used the apomict Boechera gunnisoniana, a close relative of Arabidopsis thaliana, to investigate the transcriptional basis underlying apomeiosis and parthenogenesis. Here, we present the first comprehensive reference transcriptome for reproductive development in an apomictic species. To compare sexual and apomictic development at the cellular level, we then used a combination of laser-assisted microdissection with microarray and RNA-Seq analysis. Our study yields important new insights into the transcriptional basis underlying apomixis. Cell-type specific transcriptome profiles were generated from the apomictic initial cell (2 biological replicates), surrounding sporophytic tissues (sporo_nucellus; 2 biological replicates), egg cell, central cell and synergid cells (one sample each) from the triploid pseudogamous obligate apomict Boechera gunnisoniana by heterologous hybridization on the Affymetrix ATH1 arrays.

2014-06-01 | E-GEOD-51996 | biostudies-arrayexpress

Transcription profiling by array of mouse oviduct, uterus and vagina treated with DES from new born mice to understand the mechanism of the differentiation of female reproductive tracts

Project description:Diethylstilbestrol (DES) inhibits the differentiation of female reproductive tracts during fetal and neonatal days . We examined global gene expressions in the oviduct, uterus and vagina in newborn mice with or without DES. These results suggest understanding the mechanism of the differentiation of female reproductive tracts. Keywords: ordered

2004-10-28 | E-GEOD-1886 | biostudies-arrayexpress

Transcription profiling of P. aeruginosa PA01 grown with or without human LL37

Project description:Five biological repeats of P.aeruginosa PAO1 in the absence of human LL37 and five biological repeats of P.aeruginosa presence of LL37 were grown in mineral medium in continuous-culture flow cells. Microarray experiments were done using microarray slides and protocols from TIGR on cells harvested from the biofilms after 4 days of growth.

2008-10-25 | E-FPMI-12 | biostudies-arrayexpress

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