Important role of Nfkb2 in the KrasG12D-driven carcinogenesis in the pancreas

Zonera Hassan, Christian Schneeweis, Matthias Wirth, Sebastian Müller, Claudia Geismann, Thorsten Neuß, Katja Steiger, Oliver H. Krämer, Roland M. Schmid, Roland Rad, Alexander Arlt, Maximilian Reichert, Dieter Saur, Günter Schneider

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)912-919
Number of pages8
JournalPancreatology
Volume21
Issue number5
DOIs
StatePublished - Aug 2021

Keywords

  • Kras
  • NFκB2
  • Pancreatic cancer

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