Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett's oesophagus-their association with aneuploidy and neoplastic progression.
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).
Doak
Shareen H
SH
Human Molecular Pathology Group, School of Biological Sciences, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK. s.h.doak@swansea.ac.uk
Jenkins
Gareth J S
GJ
Parry
Elizabeth M
EM
Griffiths
A Paul
AP
Baxter
John N
JN
Parry
James M
JM
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000782:Aneuploidy; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D064246:Mad2 Proteins; D008297:Male; D008679:Metaplasia; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D012737:Sex Factors
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases