NADPH oxidase activation in pancreatic cancer cells is mediated through Akt-dependent up-regulation of p22phox.

ABSTRACT: We recently showed that Nox4 NADPH oxidase is highly expressed in pancreatic ductal adenocarcinoma and that it is activated by growth factors and plays a pro-survival, anti-apoptotic role. Here we investigate the mechanisms through which insulin-like growth factor I and serum (FBS) activate NADPH oxidase in pancreatic cancer (PaCa) cells. We show that in PaCa cells, NADPH oxidase is composed of Nox4 and p22(phox) catalytic subunits, which are both required for NADPH oxidase activity. Insulin-like growth factor I and FBS activate NADPH oxidase through transcriptional up-regulation of p22(phox). This involves activation of the transcription factor NF-κB mediated by Akt kinase. Up-regulation of p22(phox) by the growth factors results in increased Nox4-p22(phox) complex formation and activatio

SUBMITTER: Edderkaoui M 

PROVIDER: S-EPMC3048665 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature