Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from WT mice and bitransgenic Pdx1-cre/Kras*A mice bearing Pancreatic Ductal Adenocarcinoma

ABSTRACT: We have carried out transcriptional profile analysis in WT MICE and bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma Mouse models faithfully simulating human cancer are valuable for genetic identification of potential drug-targets but, among them, the most advantageous for practical use in subsequent preclinical testing of candidate therapeutic regimes are those exhibiting rapid tumor development. Considering that a KRAS mutation (predominantly in codon 12, such as KRASG12D; KRAS*) occurs with high frequency (~90%) in cases of human pancreatic ductal adenocarcinoma (PDA)1, we sought to develop a mouse PDA model that would exhibit high tumor incidence and short latency by ectopic overexpression of Kras*.

ORGANISM(S): Mus musculus

PROVIDER: GSE53659 | GEO | 2014/09/01

SECONDARY ACCESSION(S): PRJNA232596

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from WT mice and bitransgenic Pdx1-cre/Kras*A mice bearing Pancreatic Ductal Adenocarcinoma

Project description:We have carried out transcriptional profile analysis in WT MICE and bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma Mouse models faithfully simulating human cancer are valuable for genetic identification of potential drug-targets but, among them, the most advantageous for practical use in subsequent preclinical testing of candidate therapeutic regimes are those exhibiting rapid tumor development. Considering that a KRAS mutation (predominantly in codon 12, such as KRASG12D; KRAS*) occurs with high frequency (~90%) in cases of human pancreatic ductal adenocarcinoma (PDA)1, we sought to develop a mouse PDA model that would exhibit high tumor incidence and short latency by ectopic overexpression of Kras*. Five WT mice and 6 bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma were used to identify key genes in the formation of panceatic malignacies

2014-09-01 | E-GEOD-53659 | biostudies-arrayexpress

Gene expression analysis between the pancreatic tissues of Pdx1-cre;Kras LSL-G12D and Pdx-cre;KrasLSL-G12D;IKK2/beta F/F mice

2012-01-24 | GSE33322 | GEO

Gene expression analysis between the pancreatic tissues of Pdx1-cre;Kras LSL-G12D and Pdx-cre;KrasLSL-G12D;IKK2/beta F/F mice

Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation. Pancreatic tissue from 4 groups of mice were used in this project: (1) the pancreas normal appearance of Pdx1-cre;KrasLSL-G12D;IKK2/beta mice, (2) the normal pancreas of Pdx1-cre;KrasLSL-G12D mice, (3) the pancreatic lesion of pancreatic intraepithelial neoplasia (PanIN) of Pdx1-cre;KrasLSL-G12D mice, and (4) the pancreatic lesion of PDAC of Pdx1-cre;KrasLSL-G12D mice. Each group included three mice. RNA samples from mouse pancreas were hybridized on GeneChip Mouse Gene 1.0 ST arrays (Affymetrix). Group (1) and group (2) were compared, and group (2), group (3) and group (4) were compared.

2012-01-24 | E-GEOD-33322 | biostudies-arrayexpress

PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance

Project description:Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA) making developmental regulators therapeutically attractive. Here, we demonstrate diverse functions for PDX1, a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of PanIN-derived PDA. Upon neoplastic transformation, the role of PDX1 changes from tumor suppressive to oncogenic. Interestingly, subsets of malignant cells lose PDX1 expression while undergoing EMT and PDX1 loss is associated with poor outcome. This stage-specific functionality arises from profound shifts in PDX1 chromatin occupancy from acinar cells to PDA. In summary, we report distinct roles of PDX1 at different stages of PDA, suggesting that therapeutic approaches against this potential target need to account for its changing functions at different stages of carcinogenesis. These findings provide insight into the complexity of PDA pathogenesis and advocate a rigorous investigation of therapeutically tractable targets at distinct phases of PDA development and progression.

2017-11-20 | GSE90775 | GEO

A Central Role for RAF-MEK-ERK Signaling in the Genesis and Maintenance of Pancreatic Ductal Adenocarcinoma.

Project description:Although KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDA), mutated KRAS remains an intractable pharmacological target. Consequently, an understanding of the RAS effector pathway(s) required for PDA maintenance is critical for improved strategies to treat this disease. Here we demonstrate that expression of BRAFV600E, but not PIK3CAH1047R, in the mouse pancreas led to PanIn lesions. Moreover, concomitant expression of BRAFV600E and TP53R270H resulted in lethal PDA. A large panel of PDA cell line panel was deployed to derive genomic classifiers of MEK inhibitor sensitivity. This classifier correctly predicted survival benefit in two novel in vivo syngeneic, orthotopic models of PDA. Consequently, we conclude that RAF?MEK?ERK signaling is central to the initiation, progression and maintenance of PDA and propose predictive biomarkers of response to MEK inhibition. These data further emphasize the value of leveraging multiple experimental systems to prioritize pathways for intervention in human PDA. RNA was extracted from human PDA cell line samples and hybridized on Affymetrix U133 plus 2.0 microarrays. The CEL files were processed using R based Bioconductor and normalized values were obtained using RMA. RNA was extracted from mouse PDA cell lines and hybridized on Affymetrix Mouse 430a 2.0 microarrays. The CEL files were processed using R based Bioconductor and normalized values were obtained using RMA.

2012-07-09 | E-GEOD-30562 | biostudies-arrayexpress

PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance [RNA-seq]

2017-11-27 | GSE91052 | GEO

Escape from Immunosurveillance in Pancreatic Cancer is Mediated by the Stromal Cell Expressing Fibroblast Activation Protein-Alpha

Project description:This study sought the basis for the failure of immunosurveillance in pancreatic ductal adenocarcinoma (PDA). The FAP+ cell was shown to be immunosuppressive in a spontaneous PDA model. Bioinformatic analyses show it to be identical to the Carcinoma-associated fibroblast (CAF). FAP+ cells were sorted from pancreatic ductal adenocarcinoma. Cells were isolated in duplicate experiments and these were analysed separately. These were compared separately to previously published publicly available CD4+ T-cell subset data (C57BL/6 mice and Foxp3-RFP mice (Line 8374) GEO accession GSE20898), and previously published FAP+ cell datasets (transgenic albino (Tyr-/-) C57BL/6 mouse, GEO accession GSE39438).

2012-11-30 | E-GEOD-42605 | biostudies-arrayexpress