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GSE42937
Homo sapiens
20 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches.
Publication Title
The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
The Carboxy-terminal domain (CTD) of RNA Polymerase II (RNAPII) in mammals undergoes extensive post-translational modification, which is essential for transcriptional initiation and elongation. Here, we show that the CTD of RNAPII is methylated at a single arginine (R1810) by the transcriptional co-activator CARM1. Although methylation at R1810 is present on the hyper-phosphorylated form of RNAPII in vivo, Ser-2 or Ser-5 phosphorylation inhibit CARM1 activity towards this site in vitro, suggesting that methylation occurs before transcription initiation. Mutation of R1810 results in the mis-expression of a variety of snRNAs and snoRNAs, an effect that is also observed in Carm1-/- MEFs. These results demonstrate that CTD methylation facilitates the expression of select RNAs, perhaps serving to discriminate the RNAPII-associated machinery recruited to distinct gene types. Overall design: To address the function of RNAPII methylation, we generated Raji cell lines expressing an RNA Polymerase II resistant to a-amanitin and carrying either wild-type R1810 or an arginine to alanine substitution at that same residue, abolishing R1810 methylation of the CTD. In cells cultured in a-amanitin, the a-amanitin-resistant mutants fully replaced the functions of endogenous RNAPII, allowing us to study if gene-expression is affected by the absence of R1810me
Publication Title
The C-terminal domain of RNA polymerase II is modified by site-specific methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers.
Publication Title
Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Origins of the brain tumor, medulloblastoma, from stem cells or restricted pro-genitor cells are unclear. To investigate this, we activated oncogenic Hedgehog signaling in multipotent and lineage-restricted CNS progenitors. We observed that normal unipo-tent cerebellar granule neuron precursors (CGNP) derive from hGFAP+ and Olig2+ rhombic lip progenitors. Hedgehog activation in a spectrum of early and late stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and that they retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hedgehog signaling promotes medulloblastoma from lineage-restricted granule cell progenitors.
Publication Title
Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
The aim of the study is to identify AR target gens in LNCaP cells Overall design: 6 samples correponding to 2 times 3 replicates were used for the study
Publication Title
Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Embryonal Tumors with Multilayered Rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh- and Wnt-signaling. Co-activation of these pathways in murine neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts based on histology and global gene expression analyses, and point to apical radial glia cells as the possible tumor cell-of-origin. Overexpression of LIN28A, which is a hallmark of human ETMRs, augments Sonic Hedgehog (Shh)- and Wnt-signaling in these precursor cells through downregulation of let7-miRNA, and LIN28A/let7a interaction with the Shh-pathway was detected at the level of Gli mRNA. Finally, human ETMR cells that were transplanted into immunocompromised host mice were responsive to the Shh-inhibitor Arsenic trioxide (ATO). Our findings provide a novel mouse model to study this tumor type, demonstrate the driving role of Wnt- and Shh-activation in the growth of ETMRs and propose downstream inhibition of Shh-signaling as a therapeutic option for patients with ETMRs.
Publication Title
A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.
Publication Title
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic and therapeutic procedures. Methods: We characterized a panel of fourteen human colon carcinoma cell lines and their corresponding xenografts for the surface expression of different potential stem cell markers: CD133, CD24, CD44, CDCP1 and CXCR4. In five cell lines and nine xenografts mRNA expression of the investigated markers was determined. Tumour growth behaviour of CD133+, CD133- and unsorted SW620 cells was evaluated in vivo. Results: All surface markers showed distinct expression patterns in the examined tumours. Analyses of the corresponding xenografts revealed a significant reduction of cell numbers expressing the investigated markers. CD44 and CXCR4 mRNA expression correlated within the cell line panel and CD44 and CDCP1 within the xenograft panel, respectively. Small subpopulations of double and triple positive cells could be described. SW620 showed significantly higher take rates and shorter doubling times in vivo when sorted for CD133 positivity. Conclusion: Our data support the hypothesis of a small subset of cells with stem cell-like properties characterized by a distinct surface marker profile. In vivo growth kinetics give strong relevance for an important role of CD133 within the mentioned surface marker profile.
Publication Title
Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
WNT-induced secreted protein 1 (WISP1/CCN4), a member of the CCN protein family, acts as a downstream factor of the canonical WNT-signaling pathway. A dysregulated expression of WISP1 often reflects its oncogenic potential by inhibition of apoptosis, a necessary form of cell death that protect cell populations for transformation into malignant phenotypes. WISP1-signaling is also known to affect proliferation and differentiation of human mesenchymal stem cells (hMSCs), which are fundamental for the constitution and maintenance of the musculoskeletal system. Our study emphasizes the importance of WISP1-signaling for cell survival of primary human cells. Therefore, we established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. We were able to demonstrate the consequence of cell death immediately after WISP1 down-regulation took place. Bioinformatical analyses of subsequent performed microarrays from WISP1 down-regulated vs. control samples confirmed this observation. We uncovered several clusters of differential expressed genes important for cellular apoptosis induction and immuno-regulatory processes, thereby indicating TRAIL-induced and p53-mediated apoptosis as well as IFNbeta-signaling. Since all of them act as potent inhibitors for malignant cell growth, in vitro knowledge about the connection with WISP1-signaling could help to find new therapeutic approaches concerning cancerogenesis and tumor growth in musculoskeletal tissues.
Publication Title
WISP 1 is an important survival factor in human mesenchymal stromal cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples