The correlation analysis of WWOX expression and cancer related genes in neuroblastoma- a real time RT-PCR study.
Neuroblastoma is one of the most common paediatric cancers, described as unpredictable due to diverse patterns of behaviour. WWOX is a tumour suppressor gene whose expression is reduced in many tumour types. Loss of its expression was shown to correlate with more aggressive disease stage and mortality rate. The aim of this study was to investigate the role of the WWOX tumour suppressor gene in neuroblastoma formation. We performed real-time RT-PCR to analyse levels of WWOX expression in 22 neuroblastic tumour samples in correlation with genes involved in cell cycle regulation (CCNE1, CCND1), proliferation (MKI67), apoptosis (BCL2, BIRC5, BAX) and signal transduction (EGFR, ERBB4). We also evaluated two potential mechanisms - promoter methylation (MethylScreen method) and loss of heterozygosity (LOH) status, which could be connected with regulation of WWOX gene expression. We found a positive correlation between WWOX gene and BCL2 and HER4 JM-a and negative with cyclin D1 and E1. Our observations are consistent with previous findings and emphasise the role of WWOX in cell cycle and apoptosis regulation. Moreover, strong positive association with HER4 JM-a in this tumour type may indicate a role for WWOX in neuroblastoma cell differentiation. The presented results indicate that LOH in locus D16S3096 (located in intron 8) may be involved in the regulation of WWOX mRNAexpression. However, no association between methylation status of WWOX promoter and its expression was observed.
Department of Molecular Cancerogenesis, Medical University of Lodz, Łódź, Poland.
Magdalena
M
Nowakowska
Department of Molecular Cancerogenesis, Medical University of Lodz, Łódź, Poland.
Elżbieta
E
Płuciennik
Department of Molecular Cancerogenesis, Medical University of Lodz, Łódź, Poland.
Wioletta I
WI
Wujcicka
Department of Pediatric Surgery and Oncology, Medical University of Lodz, Łódź, Poland.
Anna
A
Sitkiewicz
Department of Bone Marrow Transplantation, Pediatric Oncology, and Hematology, University of Medicine, Wrocław, Poland.
Bernarda
B
Kazanowska
Department of Pediatric Oncology and Hematology, Medical University of Lodz, Łódź, Poland.
Elżbieta
E
Zielińska
Department of Molecular Cancerogenesis, Medical University of Lodz, Łódź, Poland.
Andrzej K
AK
Bednarek
D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D049109:Cell Proliferation; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D010088:Oxidoreductases / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D000074584:WW Domain-Containing Oxidoreductase
D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human