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SRP058911
Homo sapiens
9 Downloadable Samples
IlluminaHiSeq2000
Description
Background and Aim: Fra-1 (Fos-related antigen-1) is a member of the AP1 (activator protein-1) family of transcription factors. We have recently shown that Fra-1 is necessary for breast cancer cells to metastasize in vivo, and that breast cancer outcome can be predicted by a classifier comprising genes that are expressed in a Fra-1-dependent fashion. Here, we show that Fra-1 plays an important role also in colon cancer progression. Methods: We compared proliferation rates of parental and Fra-1-depleted colon cancer cells in vitro under 2D, 3D, and attachment-free conditions and in vivo upon subcutaneous and intravenous injections into mice. We also compared RNA expression profiles of colon cancer cells with and without Fra-1 expression. Results: Fra-1 depletion impair colony outgrowth of human colon cancer cells in soft agar and in suspension, whereas it does not affect proliferation on 2D culture plates. Consistent with this, upon subcutaneous injection into mice, tumors formed by Fra-1-depleted colon cancer cells are only three times smaller than those produced by control cells. In contrast, when injected intravenously, Fra-1 depletion causes 200-fold reduction in tumor burden. Consistent with the more aggressive characteristics of Fra-1-proficient tumors, the prognosis of colon cancer patients can be predicted by a Fra-1 classifier generated by comparing RNA profiles of parental and Fra-1-depleted colon cancer cells. Conclusions: Our results demonstrate that Fra-1 is an important determinant of the metastatic potential of human colon cancer cells, and suggest that a Fra-1 classifier can be used as a prognostic predictor in colon cancer patients. Overall design: HT29 cell line, two shRNAs against Fra-1, one empty vector control, three biological replicates
Publication Title
Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Publication Title
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Neuroblastoma cell lines can differentiate upon retinoic acid (RA) treatment, a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen we identify the transcriptional coactivator Mastermind-like 3 (MAML3) as a gene whose ectopic expression confers resistance to RA. We find that MAML3 expression leads to loss of activation of a subset of RA target genes, which hampers RA-induced differentiation. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the retinoic acid receptor, suggesting a role for MAML3 in the regulation of these genes. In addition, MAML3 has RA independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. Our results indicate an important role for MAML3 in differentiation and proliferation of neuroblastomas. Overall design: RNA-seq of SK-N-SH control and MAML3 overexpressing (SD3.23) cells, either untreated (UT) or treated with 1 µM RA (RA).
Publication Title
Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Prostate cancer (PCa) development and progression are associated with chronic inflammation. The cytokine interleukin (IL)-6 can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL-6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, under treatment with 5 ng/ml IL-6. Interferon regulatory factor (IRF)9 was identified as one of the most prevalent IL-6 regulated genes in both cell lines. IRF9 is a mediator of type I interferon signaling and acts together with signal transduction and activator of transcription (STAT)1 and 2 to activate transcription of interferon responsive genes. The IL-6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and Western blot, respectively, in both cell lines and could be blocked by the anti-IL-6 antibody Siltuximab. Three PCa cell lines with an autocrine IL-6 loop, PC3, DU145, and LNCaP-IL-6+, showed a high expression of IRF9. A tissue microarray with 36 malignant and adjacent 36 benign areas from prostate cancer specimens showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL-6. Downregulation and overexpression of IRF9 provided evidence for an interferon-independent role of IRF9 on cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFN-2. We concluded that IL-6 is an inducer of IRF9 expression in prostate cancer and a sensitizer for the antiproliferative effects of IFN2.
Publication Title
IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9.
Sample Metadata Fields
Cell line, Treatment
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
To analyze the impact of photosynthetic redox signals, light sources with spectral qualities that preferentially excite either Photosystem I (PSI light) or Photosystem II (PSII light) were used. The light sources have been described in (Wagner et al, Planta 2008). Strong reduction signals were induced by light shifts from PSI to PSII light (PSI-II). In order to find primary regulated genes the acclimation responses were monitored at 30 min and 60 min after a light shift. The control was continuous Psi light at the same time. We used stn7 (a thylakoid redox regulated kinase) to specifically block transduction of photosynthetic redox signal in order to compare real redox regulated with that of other light acclimation pathways.
Publication Title
Identification of Early Nuclear Target Genes of Plastidial Redox Signals that Trigger the Long-Term Response of Arabidopsis to Light Quality Shifts.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes.
Publication Title
Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines.
Sample Metadata Fields
Sex, Race
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Growth factor independence genes (Gfi1 and Gfi1b) repress recombination activating genes (Rag) transcription in developing B lymphocytes. Because all blood lineages originate from hematopoietic stem cells (HSCs) and different lineage progenitors have been shown to share transcription factor networks prior to cell fate commitment, we hypothesized that GFI family proteins may also play a role in repressing Rag transcription or a global lymphoid transcriptional program in other blood lineages. We tested the level of Rag transcription in various blood cells when Gfi1 and Gfi1b were deleted, and observed an upregulation of Rag expression in plasmacytoid dendritic cells (pDCs). Using microarray analysis, we observed that Gfi1 and Gfi1b regulate a broad spectrum of cellular processes in pDCs, but not a lymphoid specific transcriptional program. This study establishes a role for Gfi1 and Gfi1b in Rag regulation in a non-B lineage cell type
Publication Title
Gfi1 and gfi1b repress rag transcription in plasmacytoid dendritic cells in vitro.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention.
Publication Title
Attenuation of allergic contact dermatitis through the endocannabinoid system.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to detect the differences in gene-expression of the periontal ligament between patients with healthy periodontal ligament and patients with periodontitis
Publication Title
The pathology of bone tissue during peri-implantitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study we want to ascertain the differences and similarities of infected and inflammated peri implant tissue versus healthy peri implant tissue at the mRNA level.
Publication Title
The pathology of bone tissue during peri-implantitis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples