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accession-icon SRP027258
Genome-wide transcriptome analysis of the dietary chemopreventive phytochemical sulforaphane on normal and prostate cancer cells.
  • organism-icon Homo sapiens
  • sample-icon 36 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Overall design: Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane

Publication Title

Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.

Sample Metadata Fields

Specimen part, Subject, Time

View Samples
accession-icon GSE57801
MMS induced expression changes
  • organism-icon Mus musculus, Drosophila melanogaster
  • sample-icon 71 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE57788
MMS induced expression changes (Drosophila)
  • organism-icon Drosophila melanogaster
  • sample-icon 36 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.

Publication Title

Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

Sample Metadata Fields

Specimen part, Treatment

View Samples
accession-icon GSE57789
MMS induced expression changes (Mouse)
  • organism-icon Mus musculus
  • sample-icon 35 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.

Publication Title

Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

Sample Metadata Fields

Specimen part, Treatment

View Samples
accession-icon SRP061705
Dosage effect on genes in maize copy-number alterations
  • organism-icon Zea mays
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

We sequenced 9 mRNA samples taken from the 14-day old maize seedling tissue. These 9 samples are comprised by 3 genotypes and 3 replications. Overall design: Examination of mRNA levels in each individual genotype.

Publication Title

Genes and Small RNA Transcripts Exhibit Dosage-Dependent Expression Pattern in Maize Copy-Number Alterations.

Sample Metadata Fields

Specimen part, Subject

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accession-icon SRP050591
A Saccharomyces cerevisiae strain with a minimal complement of glycolytic genes reveals strong redundancies in central metabolism
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

As a result of ancestral whole genome and small-scale duplication events, the genome of Saccharomyces cerevisiae's, and of many eukaryotes, still contain a substantial fraction of duplicated genes. In all investigated organisms, metabolic pathways, and more particularly glycolysis, are specifically enriched for functionally redundant paralogs. In ancestors of the Saccharomyces lineage, the duplication of glycolytic genes is purported to have played an important role leading to S. cerevisiae current lifestyle favoring fermentative metabolism even in the presence of oxygen and characterized by a high glycolytic capacity. In modern S. cerevisiae, the 12 glycolytic reactions leading to the biochemical conversion from glucose to ethanol are encoded by 27 paralogs. In order to experimentally explore the physiological role of this genetic redundancy, a yeast strain with a minimal set of 14 paralogs was constructed (MG strain). Remarkably, a combination of quantitative, systems approach and of semi-quantitative analysis in a wide array of growth environments revealed the absence of phenotypic response to the cumulative deletion of 13 glycolytic paralogs. This observation indicates that duplication of glycolytic genes is not a prerequisite for achieving the high glycolytic fluxes and fermentative capacities that are characteristic for S. cerevisiae and essential for many of its industrial applications and argues against gene dosage effects as a means for fixing minor glycolytic paralogs in the yeast genome. MG was carefully designed and constructed to provide a robust, prototrophic platform for quantitative studies, and is made available to the scientific community. Overall design: The goals of the present study are to experimentally explore genetic redundancy in yeast glycolysis by cumulative deletion of minor paralogs and to provide a new experimental platform for fundamental yeast research by constructing a yeast strain with a functional 'minimal glycolysis'. To this end, we deleted 13 minor paralogs, leaving only the 14 major paralogs for the S. cerevisiae glycolytic pathway. The cumulative impact of deleting all minor paralogs was investigated by two complementary approaches. A first, quantitative analysis focused on the impact on glycolytic flux under a number of controlled cultivation conditions that, in wild-type strains, result in different glycolytic fluxes. These quantitative growth studies were combined with transcriptome, enzyme-activity and intracellular metabolite assays to capture potential small phenotypic effects. A second, semi-quantitative characterization explored the phenotype of the 'minimal glycolysis' strain under a wide array of experimental conditions to identify potential context-dependent phenotypes

Publication Title

The Genetic Makeup and Expression of the Glycolytic and Fermentative Pathways Are Highly Conserved Within the <i>Saccharomyces</i> Genus.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE8977
Bone-marrow-derived mesenchymal stem cells promote breast cancer metastasis
  • organism-icon Homo sapiens
  • sample-icon 19 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

tumor microenviroment facilitates metastatic spread by eliciting reversible changes in the phenotypes of cancer cells

Publication Title

Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE46884
Gene Expression Signature of Human Polynucleotide Phosphorylase (hPNPaseold-35) in Melanoma
  • organism-icon Homo sapiens
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

Human Polynucleotide Phosphorylase (hPNPaseold-35) is an evolutionarily conserved 35 exoribonuclease implicated in the regulation of numerous physiological processes like maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation.

Publication Title

Identification of genes potentially regulated by human polynucleotide phosphorylase (hPNPase old-35) using melanoma as a model.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE1928
acute genes during CNS injury and their expression in cultured astrocytes
  • organism-icon Homo sapiens, Rattus norvegicus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome U34 Array (rgu34a)

Description

A robust set of CNS transcript changes was defined by comparing microarray data that describe the injury response of the rat retina [Vazquez-Chona et al., IOVS 2004; GSE1001], brain [Matzilevich et al., J Neurosci Res 2002; GSE1911], and spinal cord [Di Giovanni et al., Ann Neurol 2003; GDS63]. We determined the CNS injury genes that were expressed in cultured astrocytes from rat cortex [GSM34300] and from human optic nerve head [Yang et al., Physiol Genomics 2004; GDS532].

Publication Title

Genetic networks controlling retinal injury.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP126765
Early response of human ovarian and fallopian tube surface epithelial cells to norepinephrine
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

The purpose of this study is to understand the effects of adrenergic signaling on the transcriptome of cell line models postulated to be the cells of origin of epithelial ovarian cancers using RNA-Seq. Here we explored the effects of the stress-related hormone, norepinephrine, on normal human ovarian and fallopian tube surface epithelial cellss. We investigated the early transcriptional response to norepinephrine in normal immortalized ovarian surface epithelial cells and fallopian tube secretory cells. RNA-Seq data of treated and untreated cells were analyzed to identify genes with differential expression. Overall design: RNA-seq data from ovarian surface epithelial cells and fallopian tube epithelial cells after treatment with 1µM norepinephrine for 1 hour (or mock-treatment). Three independent replicates were performed for each condition and cell line.

Publication Title

Early transcriptional response of human ovarian and fallopian tube surface epithelial cells to norepinephrine.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

View Samples
...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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