Abstract 5358: IL-4/IL-13 induce Duox2/DuoxA2 expression and reactive oxygen production in human pancreatic and colon cancer cells

NADPH oxidase (NOX)-derived reactive oxygen species (ROS) contribute significantly to inflammation-associated carcinogenesis. Expression of dual oxidase 2 (Duox2), one of seven members of the NOX gene family, is up-regulated in inflammatory bowel disease, chronic pancreatitis, and in many human malignancies including carcinomas of the prostate, lung, and breast. Previously, we demonstrated that Stat1 and/or NF-κB play a critical role in modulating the enhanced expression of Duox2, and its cognate maturation factor DuoxA2, by IFN-γ and lipopolysaccharide in human pancreatic cancer cells. This cytokine-mediated increase in Duox2 expression is responsible for a consequent significant increase in tumor cell H2O2 production and DNA damage. Using Caco2 and T84 human colon cancer lines, and BxPC-3 pancreatic cancer cells, we now report that two other pro-inflammatory cytokines, IL-4 and IL-13, also strongly induce Duox2/DuoxA2 RNA and protein expression (>5-10-fold after 24h treatment with 50 ng/ml cytokine). In the BxPC-3 line, IL-4 exposure activates the Stat6 signaling pathway, enhances expression of Duox2/DuoxA2 in a time- and concentration-dependent manner, and leads to a significant increase in the generation of extracellular H2O2. The transcription and translation inhibitors actinomycin D and cyclohexamide both individually suppress IL-4-induced Duox2 expression, suggesting that IL-4-mediated Duox2 up-regulation is transcriptionally regulated, but that new protein synthesis...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Carcinogenesis Source Type: research