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Series GSE39969 Query DataSets for GSE39969
Status Public on Jun 30, 2014
Title NFATc1 integrates STAT3 inflammatory signals to promote Kras(G12D)-driven carcinogenesis in the pancreas.
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Inflammatory transcription networks have been linked with the development of pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that NFATc1 is both necessary and sufficient to drive progression of KrasG12D-initiated PDAC, particularly in the context of inflammation. Significantly, nuclear NFATc1 accelerates PDAC development in KrasG12D mice, whereas conditional NFATc1 deletion or pharmacological inhibition attenuates inflammation-mediated carcinogenesis. Mechanistically, NFATc1 induces STAT3 expression, complex formation and signal integration in PDAC. Genome-wide ChIP-sequencing and expression analysis in cells derived from c.n.NFATc1;KrasG12D mice identified combinatorial NFATc1/STAT3 binding at chromatin enhancer sites and subsequent regulation of key molecules involved in oncogenic signaling, growth and inflammation. Together, this study supports the relevance of inflammatory transcription factor networks in pancreatic carcinogenesis and provides a theoretical platform for therapeutic targeting of NFATc1 nucleoprotein complexes in PDAC.
Overall design NFATc1 ChIP followed by high throughput sequencing in primary murine pancreatic cancer cells (referred to as NKC cells) derived from transgenic mice with pancreas-specific constitutive activation of NFATc1 and KrasG12D mutation in the presence or absence of STAT3 shRNA; 2 ChIP samples (scramble DNA and shSTAT3 DNA) and 1 unenriched input control from the same chromatin pool.
Contributor(s) Baumgart S, Bartkuhn M, Wolf E, Ellenrieder V
Citation(s) 24694735
Submission date Aug 08, 2012
Last update date May 15, 2019
Contact name Marek Bartkuhn
Organization name Justus-Liebig-University Giessen
Department Biomedical Informatics and Systems Medicine
Street address Aulweg 132
City Giessen
State/province Hessen
ZIP/Postal code 35392
Country Germany
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (3)
GSM982509 NFATc1-ChIP-Seq-scramble
GSM982510 NFATc1-ChIP-Seq-shSTAT3
GSM982511 Input DNA
BioProject PRJNA172179
SRA SRP014743

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Supplementary file Size Download File type/resource
GSE39969_RAW.tar 575.1 Mb (http)(custom) TAR (of BED, WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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