Browse

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

Cited 55 time in Web of Science Cited 54 time in Scopus
Authors
Lee, Kyeong-sook; Lee, You-soub; Lee, Jong-min; Ito, Kosei; Cinghu, Senthilkumar; Kim, Jang-hyun; Jang, Ju-won; Li, Yinghui; Goh, Yun-mi; Chi, Xin-zi; Wee, Heejun; Lee, Hang Woong; Hosoya, Akihiro; Chung, Jin-haeng; Jang, Ja-june; Kundu, Joydeb Kumar; Surh, Young-Joon; Kim, Wun-jae; Ito, Yoshiaki; Jung, Han-sung; Bae, Sukchul
Issue Date
2010-06
Publisher
NATURE PUBLISHING GROUP
Citation
Oncogene, Vol.29 No.23, pp.3349-3361
Keywords
RUNX3lungadenocarcinomaadenomatumor suppressor
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 (similar to 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. Oncogene (2010) 29, 3349-3361; doi:10.1038/onc.2010.79; published online 15 March 2010
ISSN
0950-9232
Language
English
URI
http://hdl.handle.net/10371/76686
DOI
https://doi.org/10.1038/onc.2010.79
Files in This Item:
There are no files associated with this item.
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse