BDNF mRNA expression is significantly upregulated in vestibular schwannomas and correlates with proliferative activity.
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.
Kramer
Frauke
F
Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
Stöver
Timo
T
Warnecke
Athanasia
A
Diensthuber
Marc
M
Lenarz
Thomas
T
Wissel
Kirsten
K
D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000235:genetics* / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013223:Statistics as Topic / Q000379:methods; D018709:Statistics, Nonparametric; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
C490886:ARTN protein, human; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2