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GSE34800
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The identification of subtype-specific translocations has revolutionized diagnostics of sarcoma and provided new insight into oncogenesis. We used RNA-Seq to investigate samples diagnosed as small round cell tumors of bone, possibly Ewing sarcoma, but lacking the canonical EWSR1-ETS translocation. A new fusion was observed between the BCL6 co-repressor (BCOR) and the testis specific cyclin B3 (CCNB3) genes on chromosome X. RNA-Seq results were confirmed by RT-PCR and cloning the tumor-specific genomic translocation breakpoints. 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcomas. Gene profiling experiments indicate that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly Ewings sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this group of sarcoma and that over-expression of BCOR-CCNB3 or of a truncated CCNB3 activates S-phase in NIH3T3 cells. Thus the intrachromosomal X fusion described here represents a new subtype of bone sarcoma caused by a novel gene fusion mechanism.
Publication Title
A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Utilizing glycerol and cardiotoxin (CTX) injections in the tibialis anterior muscles of M. musculus provides models of skeletal muscle damages followed by skeletal muscle regeneration. In particular, glycerol-induced muscle regeneration is known to be associated with ectopic adipogenesis. We characterized genome-wide expression profiles of tibialis anterior muscles from wild-type mice injured by either glycerol or CTX injection. Our goal was to detect gene expression changes during the time course of glycerol-induced and CTX-induced muscle regeneration models, that can lead to ectopic adipocyte accumulation.
Publication Title
Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Altered expression of microRNAs (miRNAs), an abundant class of small non-protein-coding RNAs that mostly function as negative regulators of protein-coding gene expression, is common in cancer. Here we analyze the regulation of miRNA expression in response to estrogen, a steroid hormone that is involved in the development and progression of breast carcinomas and that is acting via the estrogen receptors (ER) transcription factors. We set out to thoroughly describe miRNA expression, by using miRNA microarrays and real time RTPCR experiments, in various breast tumor cell lines in which estrogen signaling has been induced by 17-estradiol (E2). We show that the expression of a broad set of miRNAs decreases following E2 treatment in an ER-dependent manner. We further show that enforced expression of several of the repressed miRNAs reduces E2-dependent cell growth, thus linking expression of specific miRNAs with estrogen-dependent cellular response. In addition, a transcriptome analysis revealed that the E2-repressed miR-26a and miR-181a regulate many genes associated with cell growth and proliferation, including the progesterone receptor gene, a key actor in estrogen signaling. Strikingly, miRNA expression is also regulated in breast cancers of women who had received antiestrogen neoadjuvant therapy thereby showing an estrogen-dependent in vivo regulation of miRNA expression. Overall, our data indicates that the extensive alterations in miRNA regulation upon estrogen signalling pathway plays a key role in estrogen-dependent functions and highlights the utility of considering miRNA expression in the understanding of antiestrogen resistance of breast cancer.
Publication Title
Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lipid rafts are cholesterol-rich cell signaling platforms and their physiological role can be explored by cholesterol depletion. To dress a global picture of transcriptional changes ongoing after lipid raft disruption, we performed whole-genome expression profiling in epidermal keratinocytes, a cell type which synthesizes its cholesterol in situ.
Publication Title
Transcriptional profiling after lipid raft disruption in keratinocytes identifies critical mediators of atopic dermatitis pathways.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor / interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of important signal transduction molecules. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.
Publication Title
MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma.
Publication Title
Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes ewing sarcoma growth.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia protects cancer cells from chemotherapeutic drug-induced cell death.
Publication Title
TMEM45A is essential for hypoxia-induced chemoresistance in breast and liver cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 90 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Here we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Publication Title
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The expression profiles of 64 neuroblastic tumors (mainly neuroblastoma) were determined on Affymetrix chips HG U133 Plus 2.0.
Publication Title
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling, but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs.
Publication Title
Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS.
Sample Metadata Fields
No sample metadata fields
View Samples