@article{9e15fc65971741738ec89c1520489eb8,
title = "Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model",
abstract = "Lung cancer is one of the leading cancer malignancies, with a five-year survival rate of only ∼15%. We have developed a lentiviral-vector-mediated mouse model, which enables generation of non-small-cell lung cancer from less than 100 alveolar epithelial cells, and investigated the role of IKK2 and NF-κB in lung-cancer development. IKK2 depletion in tumour cells significantly attenuated tumour proliferation and significantly prolonged mouse survival. We identified Timp1, one of the NF-κB target genes, as a key mediator for tumour growth. Activation of the Erk signalling pathway and cell proliferation requires Timp-1 and its receptor CD63. Knockdown of either Ikbkb or Timp1 by short hairpin RNAs reduced tumour growth in both xenograft and lentiviral models. Our results thus suggest the possible application of IKK2 and Timp-1 inhibitors in treating lung cancer.",
author = "Yifeng Xia and Narayana Yeddula and Mathias Leblanc and Eugene Ke and Yonghui Zhang and Eric Oldfield and Shaw, {Reuben J.} and Verma, {Inder M.}",
note = "Funding Information: We appreciate the generosity of M. Pasparakis for providing the IKK2fl/fl mouse, and T. Takeya and H. Nakajima for tissue-specific promoter plasmids. We thank L. Ouyang for assistance with microarray preparation. We also thank G. Pao, O. Singer, F. Liu, D. Morvinski, Q. Zhu and Y. Soda for advice on lentiviral vector designing and discussions, and G. Estepa for assistance with preparing frozen sections. N.Y. is supported by a fellowship from the Leona and Harry Helmsley Center for Nutritional Genomics (Salk Institute). I.M.V. is an American Cancer Society Professor of Molecular Biology, and holds the Irwin and Joan Jacobs Chair in Exemplary Life Science. This work was supported in part by grants from the National Institutes of Health, Leducq Foundation, Merieux Foundation, Ellison Medical Foundation, Ipsen/Biomeasure, Sanofi Aventis, Prostate Cancer Foundation, Department of Defense and the H.N. and Frances C. Berger Foundation. The project described was supported in part by grant number R37AI048034 from the National Institute of Allergy and Infectious Diseases, and Cancer Center Core Grant Funding Information: P30CA014195-38. This work was also supported by NIH grant number CA158191.",
year = "2012",
month = mar,
doi = "10.1038/ncb2428",
language = "English (US)",
volume = "14",
pages = "257--265",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "3",
}