Title: Characterization of a cell culture model for clinically aggressive hepatocellular carcinoma induced by chronic hypoxia
Authors: van Malenstein, Hannah ×
Verslype, Chris
Windmolders, Petra
van Eijsden, Rudy
Nevens, Frederik
van Pelt, Jos #
Issue Date: Feb-2012
Publisher: Elsevier
Series Title: Cancer Letters vol:315 issue:2 pages:178-188
Abstract: We demonstrated in an in vitro model (human HepG2 liver cells) that chronic hypoxia induced gene expression is associated with an aggressive phenotype in patients with hepatocellular carcinoma (HCC). The aim of this study was to characterize this model further using gene expression microarray, real-time PCR and immunocytochemistry. Subsequently, pathway analysis software was used to identify relevant processes. After examination, we selected 2% O(2) during 72h as conditions to study chronic hypoxia. The most affected signaling is centered on TGF-β1 and PPARα/RXRα. Cells at 2% O(2) showed a shift in expression of Epithelial-to-Mesenchymal-Transition (EMT) related genes. Furthermore, a downregulation of liver specific detoxification pathways including cytochrome P450's and glutathione-S-transferases was observed. Both up- and downregulation events within different signaling cascades indicated a cellular adaptation and the onset of a new equilibrium. The prominent role of TGF-β1- and PPARα/RXRα signaling and cell motility pathways warrants their further investigation for therapeutic targets in HCC.
ISSN: 0304-3835
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hepatology
Nucleomics Core
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science