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Homo sapiens
31 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients.
Publication Title
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Publication Title
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
GSE1847- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Hepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata
Publication Title
Effects of Boswellia serrata in mouse models of chemically induced colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling.
Publication Title
Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The NF-B pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-B response is regulated by the activation state of the IB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-B is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-B activation and the potential importance of NF-B in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-B activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo.
Publication Title
The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples GSE75789- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to such treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and -5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased of cell proliferation, and increased cell cycle arrest and apoptosis in comparison to only irradiated cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation and cell cycle regulation. To our knowledge, this is the first study to describe role of miR-338-5p in GBM and its potential to improve sensitivity of GBM to radiation.
Publication Title
MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 15 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Terminal differentiation of epidermal cells in Drosophila embryos requires the activity of a transcription factor. Svb is necessary and sufficient to induce this process. pri is a regulator of Svb activity, converting it from a repressor into an activator. To characterize the downstream Svb and pri effectors in cell morphogenesis, we performed microarrays in wt, svb -/- (no gene) and pri -/- (svb repressor) mutant conditions.
Publication Title
Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis.
Publication Title
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sample Metadata Fields
Sex, Cell line
View Samples