Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma

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• 作者：You-Soub Lee ; Jung-Won Lee ; Ju-Won Jang ; Xin-Zi Chi ; Jang-Hyun Kim ; Ying-Hui Li ; Min-Kyu Kim ; Da-Mi Kim ; Byeung-Sub Choi ; Eung-Gook Kim ; Jin-Haeng Chung ; Ok-Jun Lee ; You-Mie Lee ; Joo-Won Suh ; Linda聽Shyue聽Huey Chuang ; Yoshiaki Ito ; Suk-Chul Bae
• 刊名：Cancer Cell
• 出版年：11 November, 2013
• 年：2013
• 卷：24
• 期：5
• 页码：603-616
• 全文大小：5399 K

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Summary

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 p14^ARF/p19^Arf and p21^WAF/CIP. When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14^ARF and p21^WAF/CIP was prolonged. These results provide a missing link between oncogenic K-Ras and the p14^ARF-p53 pathway, and may explain how cells defend against oncogenic K-Ras.