Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
J Neurooncol. 2010 May;98(1):31-9. doi: 10.1007/s11060-009-0063-6. Epub 2009 Nov 25.
The expression of neurotrophic factors, such as artemin, glial cell line-derived neurotrophic factor (GDNF), neurturin, transforming growth factors (TGF)-beta1/beta2 and brain-derived neurotrophic factor (BDNF), is enhanced in vestibular schwannomas compared to peripheral nerves. Furthermore, this upregulation may correlate with mitotic activity. Vestibular schwannoma arising from Schwann cells of the vestibular nerve are mostly benign and slow-growing. Most of the pathogenic mechanisms regulating the vestibular schwannoma growth process are unknown. An impaired growth regulation and imbalance between mitosis and apoptosis can be assumed. However, molecular mechanisms interfering with regulation of the vestibular schwannoma growth also modulated by mitogenic factors have to be identified. Neurotrophic factors are involved in regulation of developmental processes in neuronal tissues and regeneration after peripheral nerve trauma and also reveal mitogenic effects on glial cell populations. Gene expression profiles of artemin, BDNF, GDNF, TGF-beta1/beta2 and Ret were determined in the vestibular schwannoma in comparison to the peripheral nerve tissues by using semiquantitative RT-PCR. The expression data were correlated to the proliferation-associated Ki-67 labelling index. A significant higher BDNF expression was observed in the vestibular schwannoma, whereas gene expression of artemin and GDNF was upregulated in peripheral nerves. The correlation between LI and BDNF, TGF-beta1 and Ret was found to be significant in the vestibular schwannoma. Our results demonstrate a coherence between BDNF expression and proliferative activity in the vestibular schwannoma. Based on these results, we propose a pivotal role for BDNF in modulating the vestibular schwannoma growth.
神经营养因子的表达,如 artemin、胶质细胞源性神经营养因子(GDNF)、neurturin、转化生长因子(TGF)-β1/β2 和脑源性神经营养因子(BDNF),在前庭神经鞘瘤中比周围神经增强。此外,这种上调可能与有丝分裂活性相关。起源于前庭神经施万细胞的前庭神经鞘瘤大多为良性且生长缓慢。调节前庭神经鞘瘤生长的大多数发病机制尚不清楚。可以假设存在生长调节受损和有丝分裂与细胞凋亡之间的失衡。然而,必须确定干扰前庭神经鞘瘤生长调节的分子机制,这些机制也受到有丝分裂因子的调节。神经营养因子参与神经元组织的发育过程的调节和周围神经损伤后的再生,并且对神经胶质细胞群也显示出有丝分裂效应。通过半定量 RT-PCR,比较前庭神经鞘瘤与周围神经组织,确定了 artemin、BDNF、GDNF、TGF-β1/β2 和 Ret 的基因表达谱。将表达数据与增殖相关的 Ki-67 标记指数相关联。在前庭神经鞘瘤中观察到显著更高的 BDNF 表达,而 artemin 和 GDNF 的基因表达在周围神经中上调。在前庭神经鞘瘤中,LI 与 BDNF、TGF-β1 和 Ret 之间的相关性具有统计学意义。我们的结果表明 BDNF 表达与前庭神经鞘瘤的增殖活性之间存在一致性。基于这些结果,我们提出 BDNF 在调节前庭神经鞘瘤生长中起关键作用。