Gene expression profiling and pathway analysis identify the integrin signaling pathway to be altered by IL-1β in human pancreatic cancer cells: Role of JNK

The pro-inflammatory cytolcine, IL-1 beta, is a critical component of the persistent inflammatory milieu that pancreatic cancer cells frequently encounter. Although several studies report diverse mechanisms responsible for this association, yet a comprehensive global analysis of the effect of IL-1 beta in these cells is not clearly evident. In this study, we performed whole genome transcriptome analysis of control and IL-1 beta treated human pancreatic MIA PaCa-2 cells, validated the most targeted pathway and evaluated the role of JNK therein. 225 Genes were up-regulated and 1215 were down-regulated and these were categorized into biological processes and cellular pathways using the PANTHER classification system. The altered genes categorized into significant biological processes that included those of cell cycle, mitosis, transport and intracellular protein trafficking. The integrin signaling pathway emerged as harboring the maximum number of differentially expressed genes. Two important genes of this pathway, namely vinculin and alpha 5-integrin were validated and both depicted significant inhibition by IL-1 beta that was prevented in the presence of JNK siRNA. In a wound healing assay. IL-1 beta increased the migratory rate of MIA PaCa-2 and Panc-1 cells that was abrogated by JNK inhibition. Additionally, vinculin and alpha-integrin siRNAs also increased the migration of these cells along the wound edge. These results suggest that in these pancreatic cancer cells. IL-1 beta inhibits components of the integrin signaling pathway in a JNK dependent manner that contributes to their increased migratory potential. Therefore, JNK might be potentially targeted to prevent the migration and invasion of pancreatic cancer cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.