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Article: Characterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers
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TitleCharacterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers
 
AuthorsLi, Y3
Nie, CJ3
Hu, L2
Qin, Y4
Liu, HB3
Zeng, TT3
Chen, L2
Fu, L2
Deng, W2
Chen, SP3
Jia, WH3
Zhang, C1 3
Xie, D3
Guan, XY2 3
 
Issue Date2010
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
CitationCancer Research, 2010, v. 70 n. 14, p. 5695-5705 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-0392
 
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.
 
ISSN0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-10-0392
 
ISI Accession Number IDWOS:000279955300006
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).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLi, Y
 
dc.contributor.authorNie, CJ
 
dc.contributor.authorHu, L
 
dc.contributor.authorQin, Y
 
dc.contributor.authorLiu, HB
 
dc.contributor.authorZeng, TT
 
dc.contributor.authorChen, L
 
dc.contributor.authorFu, L
 
dc.contributor.authorDeng, W
 
dc.contributor.authorChen, SP
 
dc.contributor.authorJia, WH
 
dc.contributor.authorZhang, C
 
dc.contributor.authorXie, D
 
dc.contributor.authorGuan, XY
 
dc.date.accessioned2010-10-31T10:38:37Z
 
dc.date.available2010-10-31T10:38:37Z
 
dc.date.issued2010
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationCancer Research, 2010, v. 70 n. 14, p. 5695-5705 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-0392
 
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-10-0392
 
dc.identifier.epage5705
 
dc.identifier.hkuros175317
 
dc.identifier.isiWOS:000279955300006
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).

 
dc.identifier.issn0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
dc.identifier.issue14
 
dc.identifier.openurl
 
dc.identifier.pmid20570897
 
dc.identifier.scopuseid_2-s2.0-77955029578
 
dc.identifier.spage5695
 
dc.identifier.urihttp://hdl.handle.net/10722/124512
 
dc.identifier.volume70
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofCancer Research
 
dc.relation.referencesReferences in Scopus
 
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 cancers
 
dc.typeArticle
 
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<contributor.author>Liu, HB</contributor.author>
<contributor.author>Zeng, TT</contributor.author>
<contributor.author>Chen, L</contributor.author>
<contributor.author>Fu, L</contributor.author>
<contributor.author>Deng, W</contributor.author>
<contributor.author>Chen, SP</contributor.author>
<contributor.author>Jia, WH</contributor.author>
<contributor.author>Zhang, C</contributor.author>
<contributor.author>Xie, D</contributor.author>
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<description.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 (&lt;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. &#169;2010 AACR.</description.abstract>
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Author Affiliations
  1. Harbin Medical University
  2. The University of Hong Kong
  3. Sun Yat-Sen University
  4. First Affiliated Hospital of Zhengzhou University