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Cited by 517

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma

Open access
Meylan, Etienne, Dooley, Alison L., Feldser, David M., Shen, Lynn, Turk, Erin, Ouyang, Chensi, Jacks, Tyler·2009·Nature

Abstract

NF-kappaB transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival. They have also been implicated in cellular transformation and tumorigenesis. However, despite extensive biochemical characterization of NF-kappaB signalling during the past twenty years, the requirement for NF-kappaB in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-kappaB pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-kappaB activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-kappaB inhibition. Furthermore, the inhibition of NF-kappaB signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-kappaB signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-kappaB inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.

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Metadata

Authors
Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., & Jacks, T.
Venue
Nature
Published
2009-10-21
Volume
462
Issue
7269
Pages
104-107
ISSN
  • 0028-0836
  • 1476-4687
OpenAlex
W2783677708
Cited by
517
References
30
FWCI
15.64
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma. https://app.cochat.ai/papers/10.1038/nature08462
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Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., & Jacks, T. (2009). Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma. Nature. https://doi.org/10.1038/nature08462

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