Interleukin-1B signalling leads to increased survival of gastric carcinoma cells through a CREB-C/EBPβ-associated mechanism
Abstract
Polymorphisms in inflammation-related genes have been associated with a risk of gastric carcinoma (GC). However, the biological mechanisms underlying these associations are still elusive. Our objective was to determine whether chronic inflammation-associated IL1Β signalling, as seen in the context of Helicobacter pylori infection, could be linked to gastric carcinogenesis by modulating the behaviour of gastric epithelial cells. The effect of IL1B was assessed by studying the expression and activation status of the IL1Β-activated transcription factors C/EBPβ and CREB in GC cell lines. Interaction between CREB and C/EBPβ was explored through interference RNA, chromatin immunoprecipitation and chemical inhibition. CREB and C/EBPβ expression was analysed in 66 samples of primary GC and in normal gastric mucosa. GC cell growth was analysed in vitro by BrdU incorporation and in vivo employing a chicken embryo chorioallantoic membrane model. We found that IL1B regulates the expression/activation status of both C/EBPβ and CREB in GC cells through an ERK1/2-dependent mechanism. Our results show that CREB is a direct transactivator of CEBPB, acting as an upstream effector in this regulatory mechanism. Furthermore, we found CREB to be ove...Continue Reading
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