Claudin-1 is a membrane protein with four transmembrane domains, that is exclusively localized at cellular tight junctions. Recent studies have reported that claudin-1 plays an important role in cancer invasion and metastasis. However, the significance of claudin-1 in pancreatic cancer is still unknown. In the present study, we investigated the role of claudin-1 expression in pancreatic cancer growth using the PANC-1 human pancreatic cancer cell line. Treatment with tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, resulted in increased detection of 89 kDa products of poly-(ADP-ribose) polymerase (PARP), a marker of apoptosis, and decreased PANC-1 cell proliferation by 23%. Expression of claudin-1 was up-regulated by TNF-alpha in a concentration-dependent manner in PANC-1 cells. PANC-1 cells treated with TNF-alpha and siRNA against claudin-1 showed a 15% increase in proliferation; i.e. the cells transfected with siRNA against claudin-1 showed resistance to TNF-alpha-induced apoptosis. These results suggest that claudin-1 expression is responsible for TNF-alpha-dependent growth signals and the proliferation of pancreatic cancer cells.