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Article: Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

TitleOverexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability
Authors
KeywordsChromosome instability
EIF-5A2 aging
Oncogene
Transgenic mouse
Issue Date2011
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/
Citation
Bmc Cancer, 2011, v. 11 How to Cite?
AbstractBackground: Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model.Methods: An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF) were isolated to further investigate molecular mechanism of eIF-5A2 in aging.Results: Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF) cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p < 0.05) resulted from an increase in the incidences of misaligned and lagging chromosomal materials, anaphase bridges, and micronuclei in the transgenic mice.Conclusion: These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability. © 2011 Chen et al; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/138957
ISSN
2015 Impact Factor: 3.265
2015 SCImago Journal Rankings: 1.627
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU7656/07M
Major State Basic Research Program of China2006CB910104
National Natural Science Foundation of China30772475
Funding Information:

This work was support by Hong Kong Research Grant Council Grant (HKU7656/07M), Grants from the Major State Basic Research Program of China (2006CB910104) and from National Natural Science Foundation of China (No. 30772475).

References

 

DC FieldValueLanguage
dc.contributor.authorChen, Men_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorDeng, HKen_HK
dc.contributor.authorDong, Sen_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorTsang, SLen_HK
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorZan, Ten_HK
dc.contributor.authorZhu, GXen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2011-09-23T05:43:07Z-
dc.date.available2011-09-23T05:43:07Z-
dc.date.issued2011en_HK
dc.identifier.citationBmc Cancer, 2011, v. 11en_HK
dc.identifier.issn1471-2407en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138957-
dc.description.abstractBackground: Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model.Methods: An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF) were isolated to further investigate molecular mechanism of eIF-5A2 in aging.Results: Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF) cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p < 0.05) resulted from an increase in the incidences of misaligned and lagging chromosomal materials, anaphase bridges, and micronuclei in the transgenic mice.Conclusion: These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability. © 2011 Chen et al; licensee BioMed Central Ltd.en_HK
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/en_HK
dc.relation.ispartofBMC Canceren_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectChromosome instabilityen_HK
dc.subjectEIF-5A2 agingen_HK
dc.subjectOncogeneen_HK
dc.subjectTransgenic mouseen_HK
dc.titleOverexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instabilityen_HK
dc.typeArticleen_HK
dc.identifier.emailHuang, JD: jdhuang@hku.hken_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailHuen, MSY: huen.michael@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityHuen, MSY=rp01336en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1471-2407-11-199en_HK
dc.identifier.scopuseid_2-s2.0-79957512522en_HK
dc.identifier.hkuros192262en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79957512522&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.spage199en_US
dc.identifier.epage199en_US
dc.identifier.isiWOS:000291934000001-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChen, M=13204327400en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridDeng, HK=7401775438en_HK
dc.identifier.scopusauthoridDong, S=35788109500en_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridTsang, SL=15722984500en_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridZan, T=40661943300en_HK
dc.identifier.scopusauthoridZhu, GX=40662234600en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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