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Citation
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HERO ID
2966007
Reference Type
Journal Article
Title
The LIM-domain only protein 4 contributes to lung epithelial cell proliferation but is not essential for tumor progression
Author(s)
Holik, AZ; Filby, CE; Pasquet, J; Viitaniemi, K; Ciciulla, J; Sutherland, KD; Asselin-Labat, ML
Year
2015
Is Peer Reviewed?
1
Journal
Respiratory Research
ISSN:
1465-9921
EISSN:
1465-993X
Volume
16
Issue
1
Page Numbers
67
Language
English
PMID
26048572
DOI
10.1186/s12931-015-0228-0
Web of Science Id
WOS:000356579500001
URL
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84934987057&doi=10.1186%2fs12931-015-0228-0&partnerID=40&md5=c7da7407ce8361d78c2edf04599643b8
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Abstract
BACKGROUND:
The lung is constantly exposed to environmental challenges and must rapidly respond to external insults. Mechanisms involved in the repair of the damaged lung involve expansion of different epithelial cells to repopulate the injured cellular compartment. However, factors regulating cell proliferation following lung injury remain poorly understood. Here we studied the role of the transcriptional regulator Lmo4 during lung development, in the regulation of adult lung epithelial cell proliferation following lung damage and in the context of oncogenic transformation.
METHODS:
To study the role of Lmo4 in embryonic lung development, lung repair and tumorigenesis, we used conditional knock-out mice to delete Lmo4 in lung epithelial cells from the first stages of lung development. The role of Lmo4 in lung repair was evaluated using two experimental models of lung damage involving chemical and viral injury. The role of Lmo4 in lung tumorigenesis was measured using a mouse model of lung adenocarcinoma in which the oncogenic K-Ras protein has been knocked into the K-Ras locus. Overall survival difference between genotypes was tested by log rank test. Difference between means was tested using one-way ANOVA after assuring that assumptions of normality and equality of variance were satisfied.
RESULTS:
We found that Lmo4 was not required for normal embryonic lung morphogenesis. In the adult lung, loss of Lmo4 reduced epithelial cell proliferation and delayed repair of the lung following naphthalene or flu-mediated injury, suggesting that Lmo4 participates in the regulation of epithelial cell expansion in response to cellular damage. In the context of K-Ras(G12D)-driven lung tumor formation, Lmo4 loss did not alter overall survival but delayed initiation of lung hyperplasia in K-Ras(G12D) mice sensitized by naphthalene injury. Finally, we evaluated the expression of LMO4 in tissue microarrays of early stage non-small cell lung cancer and observed that LMO4 is more highly expressed in lung squamous cell carcinoma compared to adenocarcinoma.
CONCLUSIONS:
Together these results show that the transcriptional regulator Lmo4 participates in the regulation of lung epithelial cell proliferation in the context of injury and oncogenic transformation but that Lmo4 depletion is not sufficient to prevent lung repair or tumour formation.
Keywords
Lung injury; Progenitor cells; Lung cancer; LMO4
Tags
IRIS
•
Naphthalene
Database Searches - Nov 2015 (private)
New Nov 2015 (private)
Database Searches
PubMed
WOS
Combined data set
Data set for title/abstract screening
Data set for full text review
Excluded – PECO criteria not met (full-text)
Supplemental material
Non-PECO routes of exposure
Mechanistic
Mechanisms of cancer
•
Mouse Lung Tumor Workshop 2014
Mouse Lung Tumor Initial Search Sept-Oct 2023
PubMed
WoS
•
Naphthalene (2021 Evidence mapping publication)
Database Searches - Nov 2015 (private)
New Nov 2015 (private)
Database Searches
PubMed
WOS
Combined data set
Data set for title/abstract screening
Data set for full text review
Excluded – PECO criteria not met (full-text)
Supplemental material
Exposure routes other than inhalation, oral, or dermal (animal studies)
Mechanistic
Mechanisms of cancer
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