NF-κB p65 and p105 implicate in interleukin 1β-mediated COX-2 expression in melanoma cells.

Abstract

Inflammatory and microenvironmental factors produced by cancer cells are thought to directly or indirectly promote cancer cell growth. Prostaglandins, including prostaglandin E2, have key roles as a microenvironment factor in influencing the development of tumors, and are produced by the rate limiting enzyme cyclooxygenase 2 (COX-2). In this study, we used canine melanoma cells treated with the proinflammatory cytokine interleukin 1β (IL-1β) and investigated the transcriptional factor nuclear factor-κB (NF-κB) signaling in IL-1β-induced COX-2 expression. IL-1β induced prostaglandin E2 release and COX-2 mRNA expression in a time- and dose-dependent manner. In the cells treated with the NF-κB inhibitors BAY11-7082 and TPC-1, IL-1β-mediated prostaglandin E2 release and COX-2 mRNA expression were inhibited. IL-1β also provoked phosphorylation of p65/RelA and p105/NF-κB1, which are members of the NF-κB families. The IL-1β-induced phosphorylation of p65 and p105 was attenuated in the presence of both NF-κB inhibitors. In melanoma cells transfected with siRNA of p65 or p105, IL-1β-mediated COX-2 mRNA expression was inhibited. These findings suggest that canonical activation of NF-κB signaling plays a crucial role for inflammatory states in melanoma cells.