Important role of Nfkb2 in the Kras^G12D-driven carcinogenesis in the pancreas

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 Kras^G12D-driven models and this requirement of Nfkb2 is mechanistically connected to proliferative pathways. In contrast, Nfκb2 is dispensable in aggressive pancreatic ductal adenocarcinoma (PDAC) models relying on the simultaneous expression of the Kras oncogene and the mutated tumor suppressor p53. Conclusions: Our data add to the understanding of context-dependent requirements of oncogenic Kras signaling during pancreatic carcinogenesis.