Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Cell. 2013 Nov 11;24(5):603-16. doi: 10.1016/j.ccr.2013.10.003.

Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma.

Author information

1
Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea.

Abstract

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.

PMID:
24229708
DOI:
10.1016/j.ccr.2013.10.003
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center