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Article: Characterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers

TitleCharacterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2010, v. 70 n. 14, p. 5695-5705 How to Cite?
Abstract
Amplification of 19q is a frequent genetic alteration in many solid tumors, and SEI1 is a candidate oncogene within the amplified region. Our previous study found that the oncogenic function of SEI1 was associated with chromosome instability. In this study, we report a novel mechanism of genomic instability involving the SEI1-SET-NM23H1 pathway. Overexpression of SEI1 was observed in 57 of 100 of esophageal squamous cell carcinoma cases. Functional study showed that SEI1 had strong tumorigenic ability, and overexpression of SEI1 could induce the genomic instability by increasing micronuclei formation and reducing the number of chromosomes. Further study found that SEI1 was able to upregulate SET expression and subsequently promote the translocation of a small amount of NM23H1 from the cytoplasm to the nucleus. Nuclear NM23H1 can induce DNA damage through its DNA nick activity. Unlike CTL attack, only a small amount of NM23H1 translocated into the nucleus (<10%) induced by the overexpression of SEI1. Further study found that the small amount of NM23H1 only induced minor DNA damage and subsequently increased genomic instability, rather than inducing irreparable DNA damage and initiating apoptosis by CTL attack. Sister chromatid exchange experiment found that the translocation of small amount of NM23H1 into the nucleus induced by the overexpressions of SEI1/SET could increase the frequency of sister chromatid exchange. In addition, overexpression of SEI1 was associated with poor prognosis of esophageal squamous cell carcinoma. Taken together, these findings define a novel mechanism of genomic instability and malignant progression in esophageal cancers, a deadly disease of increasing incidence in developed countries. ©2010 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/124512
ISSN
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30772475
30700820
30971606
Sun Yat-Sen University85000-3171311
Research Fund for the Doctoral Program of Higher Education of China20070558272
National Key Sci-Tech Special Project of China2008ZX10002-022
Funding Information:

Grants from the National Natural Science Foundation of China (30772475, 30700820 and 30971606), Sun Yat-Sen University "Hundred Talents Program" (85000-3171311), Research Fund for the Doctoral Program of Higher Education of China (20070558272), and National Key Sci-Tech Special Project of China (2008ZX10002-022).

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Yen_HK
dc.contributor.authorNie, CJen_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorQin, Yen_HK
dc.contributor.authorLiu, HBen_HK
dc.contributor.authorZeng, TTen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorChen, SPen_HK
dc.contributor.authorJia, WHen_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorXie, Den_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-10-31T10:38:37Z-
dc.date.available2010-10-31T10:38:37Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer Research, 2010, v. 70 n. 14, p. 5695-5705en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124512-
dc.description.abstractAmplification of 19q is a frequent genetic alteration in many solid tumors, and SEI1 is a candidate oncogene within the amplified region. Our previous study found that the oncogenic function of SEI1 was associated with chromosome instability. In this study, we report a novel mechanism of genomic instability involving the SEI1-SET-NM23H1 pathway. Overexpression of SEI1 was observed in 57 of 100 of esophageal squamous cell carcinoma cases. Functional study showed that SEI1 had strong tumorigenic ability, and overexpression of SEI1 could induce the genomic instability by increasing micronuclei formation and reducing the number of chromosomes. Further study found that SEI1 was able to upregulate SET expression and subsequently promote the translocation of a small amount of NM23H1 from the cytoplasm to the nucleus. Nuclear NM23H1 can induce DNA damage through its DNA nick activity. Unlike CTL attack, only a small amount of NM23H1 translocated into the nucleus (<10%) induced by the overexpression of SEI1. Further study found that the small amount of NM23H1 only induced minor DNA damage and subsequently increased genomic instability, rather than inducing irreparable DNA damage and initiating apoptosis by CTL attack. Sister chromatid exchange experiment found that the translocation of small amount of NM23H1 into the nucleus induced by the overexpressions of SEI1/SET could increase the frequency of sister chromatid exchange. In addition, overexpression of SEI1 was associated with poor prognosis of esophageal squamous cell carcinoma. Taken together, these findings define a novel mechanism of genomic instability and malignant progression in esophageal cancers, a deadly disease of increasing incidence in developed countries. ©2010 AACR.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshCarcinoma, Squamous Cell - genetics - metabolism - pathology-
dc.subject.meshEsophageal Neoplasms - genetics - metabolism - pathology-
dc.subject.meshGenomic Instability-
dc.subject.meshHistone-Lysine N-Methyltransferase - biosynthesis - genetics - metabolism-
dc.subject.meshNM23 Nucleoside Diphosphate Kinases - biosynthesis - genetics - metabolism-
dc.titleCharacterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancersen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=70&issue=14&spage=5695&epage=5705&date=2010&atitle=Characterization+of+a+novel+mechanism+of+genomic+instability+involving+the+SEI1/SET/NM23H1+pathway+in+esophageal+cancersen_HK
dc.identifier.emailFu, L: gracelfu@hku.hken_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-10-0392en_HK
dc.identifier.pmid20570897en_HK
dc.identifier.scopuseid_2-s2.0-77955029578en_HK
dc.identifier.hkuros175317en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955029578&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue14en_HK
dc.identifier.spage5695en_HK
dc.identifier.epage5705en_HK
dc.identifier.isiWOS:000279955300006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, Y=36078824800en_HK
dc.identifier.scopusauthoridNie, CJ=36463961500en_HK
dc.identifier.scopusauthoridHu, L=25958137600en_HK
dc.identifier.scopusauthoridQin, Y=7403100680en_HK
dc.identifier.scopusauthoridLiu, HB=27171509500en_HK
dc.identifier.scopusauthoridZeng, TT=37015099200en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridChen, SP=36463163900en_HK
dc.identifier.scopusauthoridJia, WH=26422262500en_HK
dc.identifier.scopusauthoridZhang, C=14033447100en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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