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Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer.

Authors
 K-S Lee  ;  Y-S Lee  ;  J-M Lee  ;  K Ito  ;  S Cinghu  ;  J-H Kim  ;  J-W Jang  ;  Y-H Li  ;  Y-M Goh  ;  X-Z Chi  ;  H Wee  ;  H-W Lee  ;  A Hosoya  ;  J-H Chung  ;  J-J Jang  ;  J K Kundu  ;  Y-J Surh  ;  W-J Kim  ;  Y Ito  ;  H-S Jung  ;  S-C Bae 
Citation
 ONCOGENE, Vol.29(23) : 3349-3361, 2010 
Journal Title
 ONCOGENE 
ISSN
 0950-9232 
Issue Date
2010
MeSH
Adenocarcinoma/etiology ; Adenocarcinoma/pathology ; Animals ; Cell Differentiation ; Cell Proliferation ; Core Binding Factor Alpha 3 Subunit/deficiency ; Core Binding Factor Alpha 3 Subunit/genetics ; Core Binding Factor Alpha 3 Subunit/physiology* ; Epithelial Cells/cytology ; Humans ; Lung/cytology* ; Lung Neoplasms/etiology ; Lung Neoplasms/pathology ; Lung Neoplasms/prevention & control* ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/analysis ; Nuclear Proteins/physiology ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins/analysis ; Proto-Oncogene Proteins/physiology ; Proto-Oncogene Proteins p21(ras)/genetics ; Pulmonary Surfactant-Associated Protein B/analysis ; Repressor Proteins/analysis ; Repressor Proteins/physiology ; Urethane/toxicity ; Uteroglobin/analysis
Abstract
Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/- mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/- bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3-/- epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+/- mice ( approximately 18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Runx3+/- mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma
Full Text
http://www.nature.com/onc/journal/v29/n23/full/onc201079a.html
DOI
10.1038/onc.2010.79
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jong Min(이종민) ORCID logo https://orcid.org/0000-0002-9466-7644
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101212
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