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The correlation analysis of WWOX expression and cancer related genes in neuroblastoma - a real time RT - PCR study

100%

Nowakowska M., Pluciennik E., Wujcicka W. I., Sitkiewicz A., Kazanowska B., Zielinska E., Bednarek A. K.

Acta Biochimica Polonica

2014

tom 61

nr 1

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.

WWOX, the tumour suppressor gene affected in multiple cancers

100%

Lewandowska U., Zelazowski M., Seta K., Byczewska M., Pluciennik E., Bednarek A. K.

Journal of Physiology and Pharmacology. Supplement

2009

tom 60

nr 1

47-56

WWOX is a tumour suppressor gene affected in multiple cancers, especially in breast, prostate and ovary. This gene is located at the chromosomal area 16q23.3-24.1, which was identified as a common chromosomal fragile site FRA16D. WWOX turned out to possess tumour suppressor features despite the fact that the most basic (classical) way of tumour suppressor gene inactivation involves both alleles (e.g. through deletions, point mutations and promoter methylation), which is very rare event in a case of WWOX, occurring only in few cell lines. A large number of papers corroborate the phenomenon of correlation between the loss of WWOX expression and more aggressive/worse prognosis in many different types of tumours, for example breast cancer, non-small cell lung cancer, bladder cancer, gastric cancer or sporadic meningiomas. Ectopically increased WWOX expression promotes migration through basal membrane, however suppresses anchorage independent growth and induces normal-like colony formation in matrigel.

Ograniczanie wyników

1 Acta Biochimica Polonica

1 Journal of Physiology and Pharmacology. Supplement

2 Bednarek A. K.

2 Pluciennik E.

1 Byczewska M.

1 Kazanowska B.

1 Lewandowska U.

1 Nowakowska M.

1 Seta K.

1 Sitkiewicz A.

1 Wujcicka W. I.

1 Zelazowski M.

1 Zielinska E.

1 2014

1 2009

Wyniki wyszukiwania

The correlation analysis of WWOX expression and cancer related genes in neuroblastoma - a real time RT - PCR study

WWOX, the tumour suppressor gene affected in multiple cancers