Publications
Detailed Information
Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice
Cited 25 time in
Web of Science
Cited 24 time in Scopus
- Authors
- Issue Date
- 2011-04
- Publisher
- ELSEVIER SCI LTD
- Citation
- DIFFERENTIATION; Vol.81, No.4, pp.261-268
- Keywords
- Runx3 ; Runx3 null mouse ; Lung adenocarcinoma ; EMT ; Lung development
- Abstract
- The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung. (C) 2011 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
- ISSN
- 0301-4681
- Language
- English
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.