KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma.

@article{Ling2012KrasG12DinducedIA,
  title={KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma.},
  author={Jianhua Ling and Ya'an Kang and Ruiying Zhao and Qianghua Xia and Dung-Fang Lee and Zhe Chang and Jin Li and Bailu Peng and Jason Fleming and Huamin Wang and Jinsong Liu and Ihor Lemischka and M -C Hung and Paul J. Chiao},
  journal={Cancer cell},
  year={2012},
  volume={21 1},
  pages={105-20}
}
Constitutive Kras and NF-κB activation is identified as signature alterations in pancreatic ductal adenocarcinoma (PDAC). However, how NF-κB is activated in PDAC is not yet understood. Here, we report that pancreas-targeted IKK2/β inactivation inhibited NF-κB activation and PDAC development in Kras(G12D) and Kras(G12D);Ink4a/Arf(F/F) mice, demonstrating a mechanistic link between IKK2/β and Kras(G12D) in PDAC inception. Our findings reveal that Kras(G12D)-activated AP-1 induces IL-1α, which, in… CONTINUE READING
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