Cancer cell, 2013-11, Vol.24 (5), p.603-616
2013
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- Autor(en) / Beteiligte
- Titel
- Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma
- Ist Teil von
- Cancer cell, 2013-11, Vol.24 (5), p.603-616
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14ARF/p19Arf and p21WAF/CIP. When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14ARF and p21WAF/CIP was prolonged. These results provide a missing link between oncogenic K-Ras and the p14ARF-p53 pathway, and may explain how cells defend against oncogenic K-Ras. [Display omitted] •Runx3 inactivation induces lung adenomas•Runx3 inactivation accelerates malignant progression of K-RasG12D-induced tumors•Runx3 activates the p14ARF-p53 pathway in a K-Ras activity-dependent manner•Restoration of Runx3 in K-Ras-activated lung cancer cell line induces apoptosis
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1535-6108eISSN: 1878-3686DOI: 10.1016/j.ccr.2013.10.003Titel-ID: cdi_proquest_miscellaneous_1751207996
- Format
- –
- Schlagworte
- Acetylation, Adenocarcinoma - metabolism, Adenocarcinoma of Lung, ADP-Ribosylation Factors - metabolism, Alveolar Epithelial Cells - physiology, Animals, Carcinogenesis - metabolism, Cell Differentiation, Cell Line, Tumor, Core Binding Factor Alpha 3 Subunit - genetics, Core Binding Factor Alpha 3 Subunit - metabolism, Cyclin D1 - metabolism, Cyclin-Dependent Kinase Inhibitor p21 - metabolism, Gene Expression, Gene Knockout Techniques, HEK293 Cells, Histone Deacetylases - metabolism, Humans, Lung Neoplasms - metabolism, Mice, Mice, Transgenic, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases - metabolism, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, Proto-Oncogene Proteins p21(ras) - genetics, Proto-Oncogene Proteins p21(ras) - metabolism, ras Proteins - genetics, ras Proteins - metabolism, Repressor Proteins - metabolism, Respiratory Mucosa - pathology