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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Xia, Y; Yeddula, N; Leblanc, M; Ke, E; Zhang, Y; Oldfield, E; Shaw, RJ; Verma, IM

Published Date

  • February 12, 2012

Published In

Volume / Issue

  • 14 / 3

Start / End Page

  • 257 - 265

PubMed ID

  • 22327365

Pubmed Central ID

  • 22327365

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

International Standard Serial Number (ISSN)

  • 1465-7392

Digital Object Identifier (DOI)

  • 10.1038/ncb2428

Language

  • eng