Linked Life Data

20570897

Source:http://linkedlifedata.com/resource/pubmed/id/20570897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-7-16
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
(c)2010 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5695-705
pubmed:meshHeading
pubmed-meshheading:20570897-Apoptosis, pubmed-meshheading:20570897-Carcinoma, Squamous Cell, pubmed-meshheading:20570897-Cell Line, Tumor, pubmed-meshheading:20570897-Cell Nucleus, pubmed-meshheading:20570897-Cytoplasm, pubmed-meshheading:20570897-Esophageal Neoplasms, pubmed-meshheading:20570897-Gene Amplification, pubmed-meshheading:20570897-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20570897-Genomic Instability, pubmed-meshheading:20570897-Histone-Lysine N-Methyltransferase, pubmed-meshheading:20570897-Humans, pubmed-meshheading:20570897-NM23 Nucleoside Diphosphate Kinases, pubmed-meshheading:20570897-Proteomics, pubmed-meshheading:20570897-Signal Transduction, pubmed-meshheading:20570897-Sister Chromatid Exchange, pubmed-meshheading:20570897-Transfection, pubmed-meshheading:20570897-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Characterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers.
pubmed:affiliation
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't