gms | German Medical Science

66th Annual Meeting of the German Society of Neurosurgery (DGNC)
Friendship Meeting with the Italian Society of Neurosurgery (SINch)

German Society of Neurosurgery (DGNC)

7 - 10 June 2015, Karlsruhe

Article

Send article

The nuclear proteins Twist-1 and Akirin-2 play an important role in the regulation of apoptotic response in glioblastomas

Meeting Abstract

Search Medline for

  • Sebastian Krossa - Zoologisches Institut, Abteilung Strukturbiologie, CAU zu Kiel
  • Anne Dorothée Schmitt - Klinik für Neurochirurgie, UKSH, Campus Kiel
  • Jürgen Fritsch - Institut für Immunologie, UKSH, Campus Kiel
  • Kirsten Hattermann - Institut für Anatomie, CAU zu Kiel
  • Maximilian Mehdorn - Klinik für Neurochirurgie, UKSH, Campus Kiel
  • Janka Held-Feindt - Klinik für Neurochirurgie, UKSH, Campus Kiel

Deutsche Gesellschaft für Neurochirurgie. 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Karlsruhe, 07.-10.06.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocP 045

doi: 10.3205/15dgnc443, urn:nbn:de:0183-15dgnc4434

Published: June 2, 2015

© 2015 Krossa 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

Text

Objective: The transcription factor Twist-1 and the interacting protein Akirin-2 are supposed to have a modulatory function in apoptotic pathways of tumors. We hypothesize that their deregulation in human gliomas might be one possible reason for the resistance of these tumors to chemotherapeutic drugs.

Method: We examined the expression of Akirin-2 and Twist-1 in solid/cultured human glioblastomas by qPCR, Western Blot and double-immunofluorescence stainings. We analyzed the temozolomide-induced regulation of both proteins by qPCR and immunocytochemistry. After generating siRNA knock-down variants, we determined altered cCaspase 3/7 activity, and cleavage of Caspase 3, 7 and PARP by Western Blot and double-immunofluorescence stainings including the ImageStream Mark II technology.

Results: Both molecules were clearly detectable in solid and cultured human glioblastomas on mRNA and protein levels. They were expressed in GFAP-positive tumor regions as well as in tumor endothelial cells and infiltrating macrophages / microglia. Expression of both molecules was highly induced after temozolomide treatment, sometimes combined with a shift of nuclear to cytosolic localization. After siRNA knock-down of Akirin-2 (with/without temozolomide treatment), higher activity of cCaspase 3/7 was observed, and higher amounts of cleaved Caspases 3, 7 and PARP were found. Immunofluorescence and ImageStream Mark II technology identified siAkirin-2 treated cells as main sources. For Twist-1 similar results were obtained with the exception that the combination of temozolomide treatment and siTwist-1 knockdown resulted in different Twist-1 cell populations with individual apoptotic responses.

Conclusions: Our results provide a basic insight into the Twist-1 and Akirin-2-mediated chemotherapeutic resistance of human gliomas.