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GSE6527
Mus musculus
72 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
The cortex and hippocampus were dissected from each individual mouse. Targets from three biological replicates of earlybird mutants and their wildtype littermates and six replicates of Rab3a knockouts and wildtype littermates were generated and the expression profiles were determined using Affymetrix MOE430 A and B arrays. Comparisons between the sample groups allow the identification of tissue specifically expressed genes and genes that are affected by mutations of Rab3a.
Publication Title
Biochemical, molecular and behavioral phenotypes of Rab3A mutations in the mouse.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
Ion Torrent Proton
Description
We previously found that the SF3A mRNA splicing complex was required for a robust innate immune response; SF3A acts in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3A1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3A in murine macrophages. Surprisingly, SF3A has substantial specificity for mRNA splicing events in innate immune signaling pathways compared to other pathways, affecting the splicing of many genes in the TLR signaling pathway to modulate the innate immune response. Overall design: RNAseq was used to monitor the effects of SF3A1 siRNA-mediated knockdown in murine macrophages. Three biological replicates were used for each of the four treatment combinations (with/without siRNA, with/without LPS). The first replicates for each combination were each sequenced in two runs, which were combined in the analysis.
Publication Title
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Targeted interference of sin3a-tgif1 function by SID decoy treatment inhibits WNT signaling and invasion in triple negative breast cancer cells. MDA-MB-231 cells were treated with scrambled SID control, 2.5M SID peptide or untreated for 24h.
Publication Title
Targeted interference of SIN3A-TGIF1 function by SID decoy treatment inhibits Wnt signaling and invasion in triple negative breast cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Here we show that in MMTV-Myc cells (1) MS culture enriches for aggressive breast cancer cells compared to the bulk cells, (2) Cbx8 knockdown reduces Notch-network gene expression. Overall design: Gene expression of (1) bulk vs MS MMTV-Myc cells, (2) control vs Cbx8 knockdown MMTV-Myc cells
Publication Title
Cbx8 Acts Non-canonically with Wdr5 to Promote Mammary Tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective of this study was to obtain expression profiles of proliferative T-HEp3-GFP and dormant D-HEp3-GFP cells after one week in vivo. The second objective was find tumor cells quiescence associated genes in dormant D-HEp3 cells that are only quiescent when injected in vivo. In this case we compared cells one week growing vs. dormant for the indicated cells in chick embryo CAMs. After one week 5 embryos per cell line carrying the indicated cells were isolated, tumors collagenased as described below and sorted for GFP-high cells usig a MoFlo machine. The sorted cells > 5x10^4 were used to extract RNA and the pure RNA was used to perform expression profiling using the Affymetrix HG-u133plus2 arrays. Because of the low amount of D-HEp3 (dormant) cells recovered all tumor cells from the dormant nodules were pooled. The same was done for proliferative-sorted T-HEp3-GFP cells to allow comparisons. Arrays were performed in triplicate.
Publication Title
NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Triple negative breast cancer (TNBC) is characterized by a poorly differentiated phenotype and limited treatment options. Aberrant epigenetics in this subtype represent a potential therapeutic opportunity, but a better understanding of the mechanisms contributing to the TNBC pathogenesis is required. The SIN3 molecular scaffold performs a critical role in multiple cellular processes, including epigenetic regulation, and has been identified as a potential therapeutic target. Using a competitive peptide corresponding to the SIN3 interaction domain of MAD (Tat-SID), we investigated the functional consequences of selectively blocking the paired amphipathic helix (PAH2) domain of SIN3. Here, we report the identification of the SID-containing adaptor PF1 as a factor required for maintenance of the TNBC stem cell phenotype and epithelial to mesenchymal transition (EMT). Tat-SID peptide blocked the interaction between SIN3A and PF1, leading to epigenetic modulation and transcriptional downregulation of TNBC stem cell and EMT markers. Importantly, Tat-SID treatment led to a reduction in primary tumor growth and disseminated metastatic disease in vivo. In support of these findings, knockdown of PF1 expression phenocopied treatment with Tat-SID both in vitro and in vivo. These results demonstrate a critical role for a complex containing SIN3A and PF1 in TNBC and provide a rational for its therapeutic targeting.
Publication Title
Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Chemotherapy resistant prostate cancer is a major clinical problem. When the prostate cancer has become androgen deprivation resistant, one of the few treatment regimens left is chemotherapy. There is a strong connection between a cancer's stem cell like characteristics and drug resistance. By performing RNA-seq we observed several factors associated with stem cells being strongly up-regulated by the estrogen receptor ß variants, ß2 and ß5. In addition, most of these factors were also up-regulated by hypoxia. One mechanism of chemotherapy resistance was expression of the hypoxia-regulated, drug transporter genes, where especially ABCG2 and MDR1 were shown to be expressed in recurrent prostate cancer and to cause chemotherapy resistance by efficiently transporting drugs like docetaxel out of the cells. Another mechanism was expression of the hypoxia-regulated notch3 gene, which causes chemotherapy resistance in urothelial carcinoma, although the mechanism is unknown. It is well known that hypoxic signaling is involved in increasing chemotherapy resistance. Regulation of the hypoxic factors, HIF-1a and HIF-2a is very complex and extends far beyond hypoxia itself. We have recently shown that two of the estrogen receptor ß variants, estrogen receptor ß2 and ß5, bind to and stabilize both HIF-1a and HIF-2a proteins leading to expression of HIF target genes. This study suggests that increased expression of the estrogen receptor ß variants, ß2 and ß5, could be involved in development of a cancer's stem cell characteristics and chemotherapy resistance, indicating that targeting these factors could prevent or reverse chemotherapy resistance and cancer stem cell expansion. Overall design: Examination of the transcriptome changed by two estrogen reseptor beta variants (ERbeta2 and ERbeta5). Control (lacking expression) and variant expressing cells in two repeats
Publication Title
The estrogen receptor variants β2 and β5 induce stem cell characteristics and chemotherapy resistance in prostate cancer through activation of hypoxic signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Triple negative breast cancers (TNBC) lacking estrogen, progesterone and HER2 receptors account for 10-20% of breast cancer and are indicative of poor prognosis. The development of effective treatment strategies therefore represents a pressing unmet clinical need. We previously identified a molecularly-targeted approach to target aberrant epigenetics of TNBC using a peptide corresponding to the SIN3 interaction domain (SID) of MAD. SID peptide selectively blocked binding of SID-containing proteins to the paired -helix (PAH2) domain of SIN3, resulting in epigenetic and transcriptional modulation of genes associated with epithelial-mesenchymal transition (EMT). To find small molecule inhibitor (SMI) mimetics of SID peptide we performed an in silico screen for PAH2 domain-binding compounds. This led to the identification of the avermectin macrocyclic lactone derivatives selamectin and ivermectin (Mectizan) as candidate compounds. Both selamectin and ivermectin phenocopied the effects of SID peptide to block SIN3-PAH2 interaction with MAD, induce expression of CDH1 and ESR1 and restore tamoxifen sensitivity in MDA-MB-231 human and MMTV-Myc mouse TNBC cells in vitro. Treatment with selamectin or ivermectin led to transcriptional modulation of genes associated with EMT and maintenance of a cancer stem cell phenotype in TNBC cells. This resulted in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo. Underlining the potential of avermectins in TNBC, pathway analysis revealed that selamectin also modulated the expression of therapeutically-targetable genes. Consistent with this, an unbiased drug screen in TNBC cells identified selamectin-induced sensitization to a number of drugs, including those targeting modulated genes.
Publication Title
Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The goal of this study was to assess whether the presence of HLA-B*35 contributes to activation of ER stress/UPR and inflammation in lcSScPAH PBMC.
Publication Title
The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients.
Sample Metadata Fields
Specimen part
View Samples