کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2108097 | 1083721 | 2013 | 14 صفحه PDF | دانلود رایگان |

SummaryHere, we report that kinase-dead IKKα knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation. IKKα reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKαlowK5+p63hi cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKKα, depleting macrophages, and reconstituting irradiated mutant animals with wild-type bone marrow (BM) prevented SCC development, suggesting that BM-derived IKKα mutant macrophages promote the transition of IKKαlowK5+p63hi cells to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs.
► We establish a robust mouse lung SCC model that resembles human lung SCCs
► IKKα reduction deregulates oncogenes, tumor suppressors, and stem cell genes
► Increased IKKα mutant macrophages promote the initiation of lung SCCs
► IKKα prevents the abnormality of squamous cells in multiple epithelial organs
Journal: - Volume 23, Issue 4, 15 April 2013, Pages 527–540