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Publication : Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model.

First Author  Xia Y Year  2012
Journal  Nat Cell Biol Volume  14
Issue  3 Pages  257-65
PubMed ID  22327365 Mgi Jnum  J:185072
Mgi Id  MGI:5427307 Doi  10.1038/ncb2428
Citation  Xia Y, et al. (2012) Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol 14(3):257-65
abstractText  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-kappaB 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-kappaB 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.
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