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GSE55488
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selenoproteins mediate the cancer-preventive properties of the essential nutrient selenium, but also have cancer-promoting effects. We examined the contributions of the 15-kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and cancer metastasis of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially the interferon-gamma-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient cells. In contrast, the Wnt/Beta-catenin pathway was up-regulated in cells that lacked both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, and controversial results of recent human clinical trials involving dietary selenium, our results are important to general public health.
Publication Title
The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selenium has cancer preventive activity that is mediated, in part, through selenoproteins. The role of the 15 kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with shRNA constructs targeting Sep15. Metabolic 75Se-labeling and Northern and Western blot analyses revealed that more than 90% of Sep15 was knocked down. Growth of the resulting Sep15-deficient CT26 cells was reduced (p<0.01) and cells formed significantly (p<0.001) fewer colonies in soft agar compared to control CT26 cells. Whereas most (14/15) BALB/c mice injected with control cells developed tumors, few (3/30) mice injected with Sep15 knockdown cells developed tumors (p<0.0001). The ability to form pulmonary metastases had similar results. Mice injected with the plasmid-transfected control cells had >250 lung metastases/mouse; however, mice injected with the Sep15 knockdown cells only had 7.8 +/- 5.4 metastases. To investigate molecular targets affected by Sep15 status, gene expression patterns between control and knockdown CT26 cells were compared. Ingenuity Pathways Analysis was used to analyze the 1045 genes that were significantly (p<0.001) affected by Sep15 deficiency. The highest scored biological functions were cancer and cellular growth and proliferation. Consistent with these observations, subsequent analyses revealed a G2/M cell cycle arrest in Sep15 CT26 knockdown cells. In contrast, to CT26 cells Sep15 knockdown in Lewis Lung Carcinoma (LLC1) cells did not affect anchorage-dependent or independent cell growth. These data suggest tissue specificity in the cancer protective effects of Sep15 knockdown, which are mediated, at least in part, by influencing the cell cycle.
Publication Title
Deficiency in the 15-kDa selenoprotein inhibits tumorigenicity and metastasis of colon cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 250 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Publication Title
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 1 Downloadable Sample
- Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profile comparison from fibroblasts of Huntington individuals and normal ones
Publication Title
Gene expression profile in fibroblasts of Huntington's disease patients and controls.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Rattus norvegicus
- 1 Downloadable Sample
- Illumina ratRef-12 v1.0 expression beadchip
Description
Comparison of the differential expression mRNA profiles from the brain cortex of hypoxia and normaixa rats by silica microarray chip
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats
Publication Title
Identification of genes influencing skeletal phenotypes in congenic P/NP rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Femoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats
Publication Title
Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 14 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Gene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder.
Publication Title
Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Ethanol exposure during prenatal development causes fetal alcohol spectrum disorder (FASD), the most frequent preventable birth defect and neurodevelopmental disability syndrome. The molecular targets of ethanol toxicity during development are poorly understood. Developmental stages surrounding gastrulation are very sensitive to ethanol exposure. To understand the effects of ethanol on early transcripts during embryogenesis, we treated zebrafish embryos with ethanol during pre-gastrulation period and examined the transcripts by Affymetrix GeneChip microarray before gastrulation. We identified 521 significantly dysregulated genes, including 61 transcription factors in ethanol-exposed embryos. Sox2, the key regulator of pluripotency and early development was significantly reduced. Functional annotation analysis showed enrichment in transcription regulation, embryonic axes patterning, and signaling pathways, including Wnt, Notch and retinoic acid. We identified all potential genomic targets of 25 dysregulated transcription factors and compared their interactions with the ethanol-dysregulated genes. This analysis predicted that Sox2 targeted a large number of ethanol-dysregulated genes. A gene regulatory network analysis showed that many of the dysregulated genes are targeted by multiple transcription factors. Injection of sox2 mRNA partially rescued ethanol-induced gene expression, epiboly and gastrulation defects. Additional studies of this ethanol dysregulated network may identify therapeutic targets that coordinately regulate early development.
Publication Title
Embryonic ethanol exposure alters expression of sox2 and other early transcripts in zebrafish, producing gastrulation defects.
Sample Metadata Fields
Treatment
View Samples