Document Detail


Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett's oesophagus-their association with aneuploidy and neoplastic progression.
MedLine Citation:
PMID:  15013707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromosomal instability (CIN) leading to aneuploidy is a ubiquitous and early event in the progression of Barrett's oesophagus, but its origins are unknown. Hence, the transcriptional levels of components of the mitotic spindle checkpoint (important in ensuring precise chromosome segregation) were examined in Barrett's lesions and correlated with the degree of aneuploidy present in the tissues. Gene expression levels of the MAD2 and BUB1 mitotic spindle checkpoint genes were assessed in 37 Barrett's patients (with histology ranging from metaplasia to adenocarcinoma) by real-time RT-PCR. In addition, the transcriptional levels of HSP27 were also examined as firstly, its expression is known to be down regulated in Barrett's metaplasia (BM) and thus was included as a positive control for the real-time RT-PCR assay. While, secondly, the expression pattern of this gene during Barrett's neoplastic progression was investigated, as this has not been previously assessed. Both over and under expression of the MAD2 and BUB1 mitotic spindle checkpoint genes were detected at all Barrett's histological stages with no apparent selective trend with neoplastic progression. In addition, no correlation with aneuploidy was established, indicating an alternative mechanism must underlie Barrett's associated chromosomal instability. HSP27 expression was reduced in metaplasia and then significantly increased with progression. Gender-related differences were observed and HSP27 expression was higher in poorly-differentiated adenocarcinomas than in well-differentiated forms. HSP27 transcriptional patterns therefore present potential as a prognostic tool to predict the aggressiveness of oesophageal adenocarcinomas (OA).
Authors:
Shareen H Doak; Gareth J S Jenkins; Elizabeth M Parry; A Paul Griffiths; John N Baxter; James M Parry
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutation research     Volume:  547     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-11     Completed Date:  2004-05-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  133-44     Citation Subset:  IM    
Affiliation:
Human Molecular Pathology Group, School of Biological Sciences, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK. s.h.doak@swansea.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics,  pathology
Aneuploidy*
Barrett Esophagus / genetics*,  pathology
Calcium-Binding Proteins / metabolism*
Cell Cycle Proteins
Cell Transformation, Neoplastic / genetics
Esophageal Neoplasms / genetics,  pathology
Female
Gene Expression*
Gene Expression Regulation, Neoplastic
HSP27 Heat-Shock Proteins
Heat-Shock Proteins*
Humans
Male
Metaplasia
Neoplasm Proteins / metabolism*
Polymerase Chain Reaction
Precancerous Conditions
Protein Kinases / metabolism*
Protein-Serine-Threonine Kinases
Repressor Proteins
Sex Factors
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Cell Cycle Proteins; 0/HSP27 Heat-Shock Proteins; 0/HSPB1 protein, human; 0/Heat-Shock Proteins; 0/MAD2L1 protein, human; 0/Neoplasm Proteins; 0/Repressor Proteins; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Bub1 spindle checkpoint protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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