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Series GSE39750 Query DataSets for GSE39750
Status Public on Apr 01, 2013
Title Programmed necrosis and apoptosis differentially regulate cancer development and biliary homeostasis in the liver
Organism Mus musculus
Experiment type Expression profiling by array
Summary For years, the term apoptosis was used synonymously for programmed cell death. However, it was recently discovered that programmed necrosis – dependent on the kinases Receptor-Interacting-Protein-Kinase (RIP)1 and RIP3 (also called necroptosis) – represents a major programmed cell-death pathway in development and immunity. At present, the functions of necroptosis in hepatitis, liver cancer development and biliary disease are unclear. Here we show that in mice with chronic hepatitis due to conditional ablation of TGF-beta-activated kinase1 (TAK1) in liver parenchymal cells (LPC), both apoptotic and necroptotic signaling pathways are activated. Strikingly, only Caspase-8-dependent apoptosis promotes spontaneous liver cancer development, while in contrast LPC necroptosis inhibits hepatic tumourigenesis. The tumour-promoting effect of apoptosis results from an induction of strong compensatory proliferation of LPC, linked with the paracrine action of growth factors like Insulin-like growth factor-2 (IGF-2) not induced by necroptosis. In addition to prevention of HCC development, induction of necroptosis leads to massive cholestasis and hyperbilirubinemia, resulting from an insufficient ductular reaction and biliary regeneration from the hepatic stem cell niche as a response to chronic hepatitis. These results indicate previously undefined distinctive functions of apoptosis and programmed necrosis in controlling cancer development and cholestasis in the liver with important implications for future therapeutic strategies in chronic liver disease.
 
Overall design 8 samples were analysed. We compared groups of 4 Tak1/Caspase8 LPC double knockout mice and 4 Tak1 LPC-KO/Rip3-/- mice to detect genes differentially regulated by apoptotic and necrotic signalling pathways.
 
Contributor(s) Denecke B, Lüdde T, Janssen J
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Submission date Jul 30, 2012
Last update date Jun 06, 2013
Contact name Bernd Denecke
E-mail(s) bernd.denecke@rwth-aachen.de
Phone +49 241 8089918
Organization name RWTH Aachen University
Department IZKF Aachen
Street address Pauwelsstrasse 30
City Aachen
State/province NRW
ZIP/Postal code 52074
Country Germany
 
Platforms (1)
GPL10740 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [probe set (exon) version]
Samples (8)
GSM978503 1_204_T_R3
GSM978504 2_205_T_R3
GSM978505 3_206_T_R3
Relations
BioProject PRJNA171577

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39750_RAW.tar 34.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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