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GSE69754
Mus musculus, Homo sapiens
14 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
In this work we investigated the combined effects of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Mouse BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.
Publication Title
VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
In this work we investigated the combined effects of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Human BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.
Publication Title
VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
Publication Title
TFEB controls vascular development by regulating the proliferation of endothelial cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 80 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
INTRODUCTION. Fixation with formalin, a widely adopted procedure to preserve tissue samples, leads to extensive degradation of nucleic acids and thereby compromises procedures like microarray-based gene expression profiling. We hypothesized that RNA fragmentation is caused by activation of RNAses during the interval between formalin penetration and tissue fixation. To prevent RNAse activation, a series of tissue samples were kept under-vacuum at 4C until fixation and then fixed at 4C, for 24 hours, in formalin followed by 4 hours in ethanol 95%.
Publication Title
Formalin fixation at low temperature better preserves nucleic acid integrity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mulcom: a multiple comparison statistical test for microarray data in Bioconductor.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip (Target ID)
Description
KRAS mutations are present at a high frequency in human cancers. The development of therapies targeting mutated KRAS requires cellular and animal preclinical models. We exploited adeno-associated virus-mediated homologous recombination to insert the KRAS G12D allele in the genome of mouse somatic cells. Heterozygous mutant cells displayed a constitutively active Kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. On the contrary, mouse cells in which we overexpressed the corresponding KRAS cDNA were readily transformed. The levels of Kras activation in knock-in cells were comparable with those present in human cancer cells carrying the corresponding mutation. KRAS-mutated cells were compared with their wild-type counterparts by gene expression profiling, leading to the definition of a "mutated KRAS-KI signature" of 345 genes. This signature was capable of classifying mouse and human cancers according to their KRAS mutational status, with an accuracy similar or better than published Ras signatures. The isogenic cells that we have developed recapitulate the oncogenic activation of Kras occurring in cancer and represent new models for studying Kras-mediated transformation. Our results have implications for the identification of human tumors in which the oncogenic KRAS transcriptional response is activated and suggest new strategies to build mouse models of tumor progression.
Publication Title
Knock-in of oncogenic Kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We noticed that a recently identified poor prognosis stem/serrated molecular subtype of colorectal cancer (CRC) is characterized by up-regulation of transcripts known to be also expressed by stromal cells. To better define the origin of such transcripts, we analyzed RNAseq and microarray datasets from CRC mouse xenografts, where human cancer cells are supported by murine stroma. The analysis revealed that mRNA levels of stem/serrated subtype genes are mostly due to stromal expression, even when the stromal fraction is below 5%. Indeed, a classifier based on genes exclusively expressed by cancer-associated fibroblasts was significantly associated, in multiple datasets, to poor prognosis of CRC and to radioresistance of rectal cancer.
Publication Title
No associated publication
Sample Metadata Fields
Disease
View Samples