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

 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 
 ONCOGENE, Vol.29(23) : 3349-3361, 2010 
Journal Title
Issue Date
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
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
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 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
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