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

TitleRunx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer
Authors
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2010, v. 29 n. 23, p. 3349-3361 How to Cite?
AbstractHuman 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 (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Run3+-/-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. © 2010 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/169568
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, KSen_US
dc.contributor.authorLee, YSen_US
dc.contributor.authorLee, JMen_US
dc.contributor.authorIto, Ken_US
dc.contributor.authorCinghu, Sen_US
dc.contributor.authorKim, JHen_US
dc.contributor.authorJang, JWen_US
dc.contributor.authorLi, YHen_US
dc.contributor.authorGoh, YMen_US
dc.contributor.authorChi, XZen_US
dc.contributor.authorWee, Hen_US
dc.contributor.authorLee, HWen_US
dc.contributor.authorHosoya, Aen_US
dc.contributor.authorChung, JHen_US
dc.contributor.authorJang, JJen_US
dc.contributor.authorKundu, JKen_US
dc.contributor.authorSurh, YJen_US
dc.contributor.authorKim, WJen_US
dc.contributor.authorIto, Yen_US
dc.contributor.authorJung, HSen_US
dc.contributor.authorBae, SCen_US
dc.date.accessioned2012-10-25T04:52:58Z-
dc.date.available2012-10-25T04:52:58Z-
dc.date.issued2010en_US
dc.identifier.citationOncogene, 2010, v. 29 n. 23, p. 3349-3361en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/169568-
dc.description.abstractHuman 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 (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Run3+-/-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. © 2010 Macmillan Publishers Limited All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshAdenocarcinoma - Etiology - Pathologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshCore Binding Factor Alpha 3 Subunit - Deficiency - Genetics - Physiologyen_US
dc.subject.meshEpithelial Cells - Cytologyen_US
dc.subject.meshHumansen_US
dc.subject.meshLung - Cytologyen_US
dc.subject.meshLung Neoplasms - Etiology - Pathology - Prevention & Controlen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshNuclear Proteins - Analysis - Physiologyen_US
dc.subject.meshProto-Oncogene Proteins - Analysis - Physiologyen_US
dc.subject.meshProto-Oncogene Proteins P21(Ras) - Geneticsen_US
dc.subject.meshPulmonary Surfactant-Associated Protein B - Analysisen_US
dc.subject.meshRepressor Proteins - Analysis - Physiologyen_US
dc.subject.meshUrethane - Toxicityen_US
dc.subject.meshUteroglobin - Analysisen_US
dc.titleRunx3 is required for the differentiation of lung epithelial cells and suppression of lung canceren_US
dc.typeArticleen_US
dc.identifier.emailJung, HS: hsjung@yuhs.acen_US
dc.identifier.authorityJung, HS=rp01683en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2010.79en_US
dc.identifier.pmid20228843-
dc.identifier.scopuseid_2-s2.0-77953480629en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953480629&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume29en_US
dc.identifier.issue23en_US
dc.identifier.spage3349en_US
dc.identifier.epage3361en_US
dc.identifier.isiWOS:000278622700004-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLee, KS=8771609600en_US
dc.identifier.scopusauthoridLee, YS=27168810200en_US
dc.identifier.scopusauthoridLee, JM=25622544900en_US
dc.identifier.scopusauthoridIto, K=36468580500en_US
dc.identifier.scopusauthoridCinghu, S=35277181000en_US
dc.identifier.scopusauthoridKim, JH=26653237500en_US
dc.identifier.scopusauthoridJang, JW=35277093300en_US
dc.identifier.scopusauthoridLi, YH=35277104900en_US
dc.identifier.scopusauthoridGoh, YM=24824651500en_US
dc.identifier.scopusauthoridChi, XZ=7006495013en_US
dc.identifier.scopusauthoridWee, H=7003796708en_US
dc.identifier.scopusauthoridLee, HW=7501482821en_US
dc.identifier.scopusauthoridHosoya, A=8651007100en_US
dc.identifier.scopusauthoridChung, JH=25621241100en_US
dc.identifier.scopusauthoridJang, JJ=7402965183en_US
dc.identifier.scopusauthoridKundu, JK=16233499400en_US
dc.identifier.scopusauthoridSurh, YJ=17234164600en_US
dc.identifier.scopusauthoridKim, WJ=8081691400en_US
dc.identifier.scopusauthoridIto, Y=26643282200en_US
dc.identifier.scopusauthoridJung, HS=7403030195en_US
dc.identifier.scopusauthoridBae, SC=7202714699en_US
dc.identifier.citeulike6870624-

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