0000000000276741
AUTHOR
Roland M. Schmid
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-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 w…
Important role of Nfkb2 in the KrasG12D-driven carcinogenesis in the pancreas
Abstract Background Oncogenic Kras initiates and drives carcinogenesis in the pancreas by complex signaling networks, including activation of the NFκB pathway. Although recent evidence has shown that oncogenic gains in Nfκb2 collaborate with Kras in the carcinogenesis, no data at the level of genetics for the contribution of Nfκb2 is available so far. Methods We used Nfkb2 knock-out mice to decipher the role of the gene in Kras-driven carcinogenesis in vivo. Results We show that the Nfkb2 gene is needed for cancer initiation and progression in KrasG12D-driven models and this requirement of Nfkb2 is mechanistically connected to proliferative pathways. In contrast, Nfκb2 is dispensable in agg…
Pattern of secondary genomic changes in pancreatic tumors ofTgfα/Trp53+/−transgenic mice
Trp53+/− mice overexpressing Tgfα in a pancreas-specific manner represent a well-established animal model for pancreatic cancer. In this study we analyzed 38 pancreatic adenocarcinomas of these mice for secondary genomic changes by comparative genomic hybridization (CGH), loss of heterozygosity (LOH) analysis, real-time PCR, and methylation-specific analysis. CGH screening of the tumors revealed a recurrent pattern of genomic changes. In more than 50% of the tumors, chromosome 11 was affected. The gain of the proximal part spans about 16 cM, including the genes for Egfr, Rel, and Stk10. The distal part of chromosome 11, which contains the Trp53 locus, was deleted. LOH analysis proved that a…