NF-?B p65 and p105 implicate in interleukin 1?-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 1? (IL-1?) and investigated the transcriptional factor nuclear factor-?B (NF-?B) signaling in IL-1?-induced COX-2 expression. IL-1? induced prostaglandin E2 release and COX-2 mRNA expression in a time- and dose-dependent manner. In the cells treated with the NF-?B inhibitors BAY11-7082 and TPC-1, IL-1?-mediated prostaglandin E2 release and COX-2 mRNA expression were inhibited. IL-1? also provoked phosphorylation of p65/RelA and p105/NF-?B1, which are members of the NF-?B families. The IL-1?-induced phosphorylation of p65 and p105 was attenuated in the presence of both NF-?B inhibitors. In melanoma cells transfected with siRNA of p65 or p105, IL-1?-mediated COX-2 mRNA expression was inhibited. These findings suggest that canonical activation of NF-?B signaling plays a crucial role for inflammatory states in melanoma cells.

SUBMITTER: Kitanaka N 

PROVIDER: S-EPMC6298655 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature