Department of Molecular Cancerogenesis, Medical University of Lodz, Mazowiecka St 6/8, 92-215 Lodz, Poland.
J Neurooncol. 2011 Jan;101(2):207-13. doi: 10.1007/s11060-010-0254-1. Epub 2010 Jun 10.
Glioblastoma multiforme is the most common type of primary brain tumor in adults. WWOX is a tumor suppressor gene involved in carcinogenesis and cancer progression in many different neoplasms. Reduced WWOX expression is associated with more aggressive phenotype and poor patient outcome in several cancers. We investigated alternations of WWOX expression and its correlation with proliferation, apoptosis and signal trafficking in 67 glioblastoma multiforme specimens. Moreover, we examined the level of WWOX LOH and methylation status in WWOX promoter region. Our results suggest that loss of heterozygosity (relatively frequent in glioblastoma multiforme) along with promoter methylation may decrease the expression of this tumor suppressor gene. Our experiment revealed positive correlations between WWOX and Bcl2 and between WWOX and Ki67. We also confirmed that WWOX is positively correlated with ErbB4 signaling pathway in glioblastoma multiforme.
多形性胶质母细胞瘤是成人中最常见的原发性脑肿瘤。WWOX 是一种肿瘤抑制基因,参与多种不同肿瘤的致癌作用和癌症进展。在几种癌症中,WWOX 表达降低与侵袭性表型和患者预后不良相关。我们研究了 67 例多形性胶质母细胞瘤标本中 WWOX 表达的改变及其与增殖、凋亡和信号转导的相关性。此外,我们还检查了 WWOX 基因缺失和启动子区甲基化状态。我们的结果表明,杂合性缺失(在多形性胶质母细胞瘤中相对常见)以及启动子甲基化可能会降低这种肿瘤抑制基因的表达。我们的实验还揭示了 WWOX 与 Bcl2 之间以及 WWOX 与 Ki67 之间呈正相关。我们还证实,在多形性胶质母细胞瘤中,WWOX 与 ErbB4 信号通路呈正相关。