Thymosin beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation

Abstract

BACKGROUND. Thymosin beta 4 (Tβ4) has been shown to be associated with tumor metastasis and angiogenesis; however, its role in pancreatic cancer has not been understood. In the current study, we examined the expression of Tβ4 in pancreatic cancer cells, and determined the effect of exogenous Tβ4 on cytokine secretion, and signal transduction in human pancreatic cancer cells. METHODS. The mRNA levels of Tβ4 were determined by real-time RT PCR. Phosphorylation of JNK in pancreatic cancer cells was determined using Bio-Plex phosphoprotein assay. The expression of cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay. RESULTS. Pancreatic cancer cell lines expressed higher amount of Tβ4 mRNA than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous Tβ4 increased the secretion of proinflammatory cytokines IL-6, IL-8 and MCP-1 in Panc-1 cells. In addition, Tβ4 activated Jun N-terminal Kinase (JNK) signaling pathways in pancreatic cancer cells. CONCLUSIONS. Tβ4 might be involved in stimulating human pancreatic cancer progression by promoting proinflammatory cytokine environment and activating JNK signaling pathway. Targeting Tβ4 and related molecules may be a novel therapeutic strategy for pancreatic cancer.