Abstract
The expression of neurotrophic factors, such as artemin, glial cell line-derived neurotrophic factor (GDNF), neurturin, transforming growth factors (TGF)-β1/β2 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-β1/β2 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-β1 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.
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The authors thank the Department of Pathology, Director Prof. Dr. H. Kreipe, for kindly providing the tumour tissues and for support in immunohistochemistry, P. Erfurt for technical assistance, and B. Vaske for help in statistical analysis.
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Kramer, F., Stöver, T., Warnecke, A. et al. BDNF mRNA expression is significantly upregulated in vestibular schwannomas and correlates with proliferative activity. J Neurooncol 98, 31–39 (2010). https://doi.org/10.1007/s11060-009-0063-6
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DOI: https://doi.org/10.1007/s11060-009-0063-6