GADD45alpha 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-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.
Schneider
Günter
G
Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
Weber
Andreas
A
Zechner
Ulrich
U
Oswald
Franz
F
Friess
Helmut M
HM
Schmid
Roland M
RM
Liptay
Susanne
S
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D051550:I-kappa B Kinase; D016328:NF-kappa B; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins