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Article: Transgenic CHD1L expression in mouse induces spontaneous tumors

TitleTransgenic CHD1L expression in mouse induces spontaneous tumors
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2009, v. 4 n. 8 How to Cite?
AbstractBackground: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.
Persistent Identifierhttp://hdl.handle.net/10722/68167
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Men_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorTsang, SLen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-09-06T06:02:00Z-
dc.date.available2010-09-06T06:02:00Z-
dc.date.issued2009en_HK
dc.identifier.citationPlos One, 2009, v. 4 n. 8en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68167-
dc.description.abstractBackground: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsP L o S One. Copyright © Public Library of Science.en_HK
dc.subject.meshCell Cycle - physiology-
dc.subject.meshChromosome Mapping-
dc.subject.meshDNA Helicases - genetics - physiology-
dc.subject.meshDNA-Binding Proteins - genetics - physiology-
dc.subject.meshLiver Neoplasms, Experimental - chemically induced - genetics - pathology-
dc.titleTransgenic CHD1L expression in mouse induces spontaneous tumorsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=4&issue=8&spage=e6727&epage=&date=2009&atitle=Transgenic+CHD1L+expression+in+mouse+induces+spontaneous+tumorsen_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0006727en_HK
dc.identifier.pmid19701453en_HK
dc.identifier.pmcidPMC2726430-
dc.identifier.scopuseid_2-s2.0-69249208771en_HK
dc.identifier.hkuros166057en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-69249208771&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue8en_HK
dc.identifier.spagee6727-
dc.identifier.epagee6727-
dc.identifier.isiWOS:000269268300007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, M=13204327400en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridHu, L=34770075600en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridTsang, SL=15722984500en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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