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GSE20271
Homo sapiens
171 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The behavior of breast cancers and their response to different chemotherapy treatments depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Publication Title
Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer.
Sample Metadata Fields
Age, Race
View Samples- Escherichia coli
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
As part of our studies on the biological functions of polyamines we have used a mutant of Escherichia coli that lacks all the genes for polyamine biosynthesis for a global transcription analysis on the effect of added polyamines. The most striking early response to polyamine addition is the increased expression of the genes for the glutamate dependent acid resistance system (GDAR) that is essential for the survival of bacteria when passing through the acid environment of the stomach. Not only were the two genes for glutamate decarboxylases (gadA and gadB) and the gene for glutamate --aminobutyrate antiporter (gadC) induced by polyamine addition, but also the various genes involved in the regulation of this system were induced. We confirmed the importance of polyamines for the induction of the GDAR system by direct measurement of glutamate decarboxylase activity and acid-survival. Effects of deletions of the regulatory genes in the GDAR system and on the effects of overproduction of two of these genes were also studied. Strikingly, overproductions of the alternate sigma factor rpoS and of the regulatory gene gadE resulted in very high levels of glutamate decarboxylase and almost complete protection against acid stress even in the absence of any polyamines. Thus, these data show that a major function of polyamines in E. coli is protection against acid stress by increasing the synthesis of glutamate decarboxylase, presumably by increasing the levels of the rpoS and gadE regulators.
Publication Title
Polyamines are critical for the induction of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli.
Sample Metadata Fields
Treatment
View Samples- Escherichia coli
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Glutathionylspermdine synthetase/amidase (Gss) and the encoding gene (gss) have only been described in two widely separated species; namely Escherichia coli and several members of the Kinetoplastida phyla. In the present paper we have studied the species distribution more extensively. It is striking that all of the 75 Enterobacteria species that has been sequenced contain sequences with very high degree of homology to the E. coli Gss protein. Although homologous sequences are also present in various other bacteria, in contrast to Enterobacteria they are not present in all species of a given phyla. As previously reported homologous sequences were found in all five species of Kinetoplastids tested (including Trypansosma cruzi), but it is striking that comparable sequences are not found in a variety of invertebrate and vertebrate species, Archea and plants. Studies in E. coli show that the highest accumulation of glutathionylspermidine is found in stationary phase cultures where most of the intracellular spermidine is converted to glutathionylspermidine. However, even in log phase cells there is some formation of glutathionylspermidine, and isotope exchange experiments show that there is a rapid exchange between glutathionylspermidine and intracellular spermidine. We have not been able to define a specific physiologic function for glutathionylspermidine, but microarray studies comparing gss+ and -gss strains of E. coli show that a large number of genes are either upregulated or downregulated by the loss of the gss gene.
Publication Title
Escherichia coli glutathionylspermidine synthetase/amidase: phylogeny and effect on regulation of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA (siRNA) targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-kappaB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD. We found that both DAP12 knockdown and control clones were capable of equally responding to phorbol 12-myristate 13-acetate (PMA), a known inducer of morphological differentiation of THP-1 cells, by exhibiting almost similar gene expression profiles between both, following a 24-hour exposure to 50 nM PMA.
Publication Title
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA (siRNA) targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-kappaB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD.
Publication Title
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Escherichia coli
- 24 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
To study the physiological roles of polyamines, we have carried out a global microarray analysis on the effect of adding polyamines to an Escherichia coli mutant that lacks polyamines because of deletions in the genes in the polyamine biosynthetic pathway. Previously, we have reported that the earliest response to the polyamine addition is the increased expression of the genes for the glutamate dependent acid resistance system (GDAR). We also presented preliminary evidence for the involvement of rpoS and gadE regulators. In the current study further confirmation of the regulatory roles of rpoS and gadE is shown by a comparison of genome-wide expression profiling data from a series of microarrays comparing the genes induced by polyamine addition to polyamine-free rpoS+/gadE+ cells with genes induced by polyamine addition to polyamine-free rpoS and gadE cells. The results indicate that most of the genes in the E. coli GDAR system that are induced by polyamines require rpoS and gadE. Our data also show that, gadE is the main regulator of GDAR and other acid-fitness-island genes. Both polyamines and rpoS are necessary for the expression of gadE genes from the three promoters of gadE (P1, P2 and P3). The most important effect of polyamine addition is the very rapid post-transcriptional increase in the level of RpoS sigma factor. Our current hypothesis is that polyamines increase the level of RpoS protein, and that this increased RpoS level is responsible for the stimulation of gadE expression, which in turn induces the GDAR system in E. coli.
Publication Title
Polyamines Stimulate the Level of the σ38 Subunit (RpoS) of Escherichia coli RNA Polymerase, Resulting in the Induction of the Glutamate Decarboxylase-dependent Acid Response System via the gadE Regulon.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 marks genes expressed in the germline with methylated Lys36 on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosomes. The DRM complex, which includes E2F/DP and Retinoblastoma homologs, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 or the DRM subunit lin-54 oppositely skew target transcript levels and cause sterility; a double mutant restores near wild-type transcript levels and germ cell development. Together, yin-yang regulation by MES-4 and DRM ensures transcript levels appropriate for germ cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.
Publication Title
Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hyperthermia (HT) treatments in combination with either chemotherapy, radiotherapy or both are used for patients with cancer in various organs. However, the acquisition of thermotolerance in cancer cells due to the increase in cytoprotective proteins attenuates the therapeutic effects of HT. BAG3 (BCL2-associated athanogene 3) is a cytoprotective protein that acts against various stresses including heat stress. Recently, we demonstrated that the inhibition of BAG3 improves cell death sensitivity to HT in cancer cells. However, a detailed molecular mechanism involved in the enhancement of HT sensitivity by BAG3-knockdown (KD) in cancer cells is unclear.
Publication Title
Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hyperthermia (HT) is widely used to treat patients with various cancers. In general, HT elicits a wide spectrum of stress responses, such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown.
Publication Title
Identification of common gene networks responsive to mild hyperthermia in human cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hyperthermia (HT) is widely used to treat patients with various cancers. In general, HT elicits a wide spectrum of stress responses such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown.
Publication Title
Identification of common gene networks responsive to mild hyperthermia in human cancer cells.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment
View Samples