GADD45α is highly expressed in pancreatic ductal adenocarcinoma cells and required for tumor cell viability

Pancreatic ductal adenocarcinoma is one of the most common causes of cancer death in the western civilization. Recently, NF-κB has been shown to be activated in pancreatic ductal adenocarcinoma through constitutive activation of IκB kinase (IKK). Inhibition of NF-κB by a super-inhibitor of NF-κB-delta-N-IκBα-resulted in impaired proliferation and induction of apoptosis, suggesting an important role of NF-κB in pancreatic tumorigenesis. Downstream target genes of IκBα have not been elucidated in pancreatic ductal adenocarcinoma in detail. Using expression profiling by cDNA array analysis of pancreatic ductal adenocarcinoma cell lines stably transfected with super-IκBα, we identified GADD45α as a significant regulated gene. GADD45α is overexpressed in pancreatic ductal adenocarcinoma at the mRNA and protein level. Using RNAi we show that downregulation of GADD45α reduces proliferation and induces apoptosis in pancreatic cancer cells. These findings provide evidence that GADD45α contributes to pancreatic cancer cell proliferation and viability.