gms | German Medical Science

67th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Korean Neurosurgical Society (KNS)

German Society of Neurosurgery (DGNC)

12 - 15 June 2016, Frankfurt am Main

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The Ran signaling pathway is upregulated dependent from glioma grade and radiochemotherapy

Meeting Abstract

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  • Sergej Telentschak - Department of Neurosurgery, University of Cologne, Germany
  • Gabriele Röhn - Department of Neurosurgery, University of Cologne, Germany
  • Stefan Grau - Department of Neurosurgery, University of Cologne, Germany
  • Boris Krischek - Department of Neurosurgery, University of Cologne, Germany
  • Roland Goldbrunner - Department of Neurosurgery, University of Cologne, Germany
  • Marco Timmer - Department of Neurosurgery, University of Cologne, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocP 015

doi: 10.3205/16dgnc390, urn:nbn:de:0183-16dgnc3908

Published: June 8, 2016

© 2016 Telentschak et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Numerous studies on different non-brain cancers indicate Ran (Ras-related nuclear protein), a key protein in the nucleoplasmic transport during interphase and the regulation of mitotic spindle formation, to be involved in tumorigenesis, cancer progression and tumor cell survival. It further is predictive for poor outcome. Overexpression of Ran has been reported in glioblastoma tissue. To further evaluate the role of the Ran signaling pathway in astrocytoma, we measured the expression of its key components Ran, RCC1, RANBP1 and RANBP2 in different types of brain tumor tissue.

Method: Using qRT-PCR and Western blot analysis the gene and protein expression was analyzed in 80 tissue samples. The tissue subtypes were astrocytomas WHO II°, anaplastic astrocytomas, primary and secondary glioblastomas and tissue samples after recurrence subsequent to radiochemotherapy. Peritumoral brain tissue was used as a control. For PCR analysis at least 10 glioma probes and for Western blot analysis at least 6 glioma probes were used per group.

Results: Ran protein overexpression compared to non-neoplastic brain was detected in anaplastic astrocytomas (90%), primary glioblastoma (140%) and secondary glioblastoma (170%). With increasing WHO grade there was an increase of Ran mRNA expression and chemo-radiation therapy led to further enhanced expression in primary and secondary glioblastoma (from 1.36 to 2.25 and from 2.08 to 3.08 arbitrary unites [AU], respectively). There was also an increase in gene expression of RCC1, RANBP1 and RANBP2 analogue to that of Ran: showing a steady increase with higher WHO grading. Correspondingly to Ran, gene expression of RCC1 increased in primary and secondary glioblastoma recurrent after radiochemotherapy from 3.19 to 3.87 AU and from 4.14 to 10.11 AU respectively as well as that of RANBP2 from 2.36 to 5.14 AU and from 2.77 to 4.74 AU respectively.

Conclusions: Our data clearly show a grade dependent upregulation of key components of the Ran pathway in astrocytomas and a further increase after radiochemotherapy. Therefore, this pathway may represent a future target for glioblastoma therapy.