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Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer.
- Source :
- Oncogene; 6/10/2010, Vol. 29 Issue 23, p3349-3361, 13p, 4 Diagrams, 2 Graphs
- Publication Year :
- 2010
-
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 (∼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. [ABSTRACT FROM AUTHOR]
- Subjects :
- EPITHELIAL cells
LUNG aging
LUNG cancer
ADENOCARCINOMA
TUMORS
HYPERPLASIA
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 29
- Issue :
- 23
- Database :
- Complementary Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 51313418
- Full Text :
- https://doi.org/10.1038/onc.2010.79