GADD45alpha is highly expressed in pancreatic ductal adenocarcinoma cells and required for tumor cell viability

Abstract

Pancreatic ductal adenocarcinoma is one of the most common causes of cancer death in the western civilization. Recently, NF-kappaB has been shown to be activated in pancreatic ductal adenocarcinoma through constitutive activation of IkappaB kinase (IKK). Inhibition of NF-kappaB by a super-inhibitor of NF-kappaB--delta-N-IkappaBalpha--resulted in impaired proliferation and induction of apoptosis, suggesting an important role of NF-kappaB in pancreatic tumorigenesis. Downstream target genes of IkappaBalpha 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-IkappaBalpha, we identified GADD45alpha as a significant regulated gene. GADD45alpha is overexpressed in pancreatic ductal adenocarcinoma at the mRNA and protein level. Using RNAi we show that downregulation of GADD45alpha reduces proliferation and induces apoptosis in pancreatic cancer cells. These findings provide evidence that GADD45alpha contributes to pancreatic cancer cell proliferation and viability.