کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2108097 1083721 2013 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Pivotal Role of IKKα in the Development of Spontaneous Lung Squamous Cell Carcinomas
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The Pivotal Role of IKKα in the Development of Spontaneous Lung Squamous Cell Carcinomas
چکیده انگلیسی

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

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 23, Issue 4, 15 April 2013, Pages 527–540
نویسندگان
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