Filters
Technology
Platform
GSE58969
Mus musculus
3 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into -cells. The induced -cells resemble islet -cells in morphology and histology, express genes essential for -cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.
Publication Title
Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of the study was to evaluate the influence of mutations in MLK4 on the protein function and the process of tumorigenesis in colorectal cancers. Biochemical data imply that a majority of MLK4 mutations in colon cancer are loss-of-function, including, E314K and Y330H mutations.
Publication Title
Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells and tumour initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-kB pathway can drive dedifferentiation of intestinal cells lacking Apc.
Publication Title
TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells and tumour initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-kB pathway can drive dedifferentiation of intestinal cells lacking Apc.
Publication Title
TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In order to identify transcriptional targets of ATF2, we used a recombinant adenovirus to express constitutively active ATF2 in murine hepatoblasts. Expression of GFP was the control condition.
Publication Title
JNK suppresses tumor formation via a gene-expression program mediated by ATF2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Mus musculus, Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Publication Title
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pancreatic neuroendocrine tumor (PanNET) is relatively infrequent but is nevertheless metastatic. Seeking to extend a new paradigm of personalized medicine, we performed an integrative analysis of transcriptomic (mRNA and microRNA) and mutational profiles and defined three clinically relevant human PanNET subtypes. Importantly, cross-species analysis revealed two of these three subtypes in a well-characterized, genetically engineered mouse model (RIP1-Tag2) of PanNET and its cell lines. Each subtype share similarities to distinct cell types in pancreatic neuroendocrine development, features are reflected in their metabolic profiles. Subtype-specific molecular signatures metabolites are proposed to identify these subtypes.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pancreatic neuroendocrine tumor (PanNET) is relatively infrequent but is nevertheless metastatic. Seeking to extend a new paradigm of personalized medicine, we performed an integrative analysis of transcriptomic (mRNA and microRNA) and mutational profiles and defined three clinically relevant human PanNET subtypes. Importantly, cross-species analysis revealed two of these three subtypes in a well-characterized, genetically engineered mouse model (RIP1-Tag2) of PanNET and its cell lines. Each subtype share similarities to distinct cell types in pancreatic neuroendocrine development, features are reflected in their metabolic profiles. Subtype-specific molecular signatures metabolites are proposed to identify these subtypes.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Specimen part
View Samples