dc.contributor.advisor | Kermer, Pawel Prof. Dr. | |
dc.contributor.author | Müther, Michael | |
dc.date.accessioned | 2016-07-15T09:09:21Z | |
dc.date.available | 2016-08-08T22:50:05Z | |
dc.date.issued | 2016-07-15 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0028-87C2-D | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5741 | |
dc.language.iso | deu | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.ddc | 610 | de |
dc.title | Zur Rolle des Co-Chaperons BAG-1 im Glioblastoma-multiforme-Zellkulturmodell | de |
dc.type | doctoralThesis | de |
dc.title.translated | Role of Co-Chaperone BAG-1 in Glioma | de |
dc.contributor.referee | Stockhammer, Florian PD Dr. | |
dc.date.examination | 2016-08-01 | |
dc.description.abstracteng | Glioblastoma multiforme (GBM) is one of the most malignant brain neoplasias and the most common primary brain tumor in adults with a very poor prognosis. Many molecular pathologies have been found to account for GBM growth.
BAG-1 (bcl-2 associated athanogene 1) is a multifunctional protein. As a member of the co-chaperone family it helps stabilize misfolded proteins and affects various cellular functions and cancer related molecular pathways. Malignancies commonly show high levels of BAG-1 protein. Until now less is known about BAG-1 in GBM.
Methods:
BAG-1 protein level was down-regulated in established GBM cell lines G112, U251 and U87G by using siRNA transfection. Proliferation was assessed by crystal violet and WST-1 proliferation assays. Toxicity was measured using ToxiLight® Bioassay. Flow Cytometry was used to investigate cell cycle changes. Experimental ionizing radiation was applied for testing radiosensitivity. Autophagy and proteasomal function were evaluated using LC3-II Western Blotting and proteasome assays.
Results:
BAG-1 significantly reduces GBM growth. This effect becomes more obvious in stress conditions such as serum starvation. Cytotoxicity and cell cycle distribution are not significantly affected by BAG-1 siRNA transfection. BAG-1 protein level does not affect radiosensitivity in GBM cells. BAG-1 increases the macroautphagic flux, no significant impact on proteasomal function was found.
Conslusion:
To improve current therapies it is becoming increasingly important to draw a most precise picture of GBM pathology. For a long time BAG-1 was thought to be an anti-apoptotic protein. In this work BAG-1 reduces GBM growth most likely by sensitizing towards apoptosis. The role of protein degradation mechanisms in GBM is poorly understood. This work provides first data on the impact of BAG-1 on autophagy and proteasomal function in GBM.
Further work needs to be done to evaluate the role of BAG-1 in GBM diagnostics and therapy. | de |
dc.contributor.coReferee | Mausberg, Rainer Prof. Dr. | |
dc.subject.ger | Glioblastoma multiforme | de |
dc.subject.ger | BAG-1 | de |
dc.subject.ger | Autophagie | de |
dc.subject.ger | Proteasomale Funktion | de |
dc.subject.ger | Co-Chaperon | de |
dc.subject.eng | Glioma | de |
dc.subject.eng | BAG-1 | de |
dc.subject.eng | Autophagy | de |
dc.subject.eng | Proteasomal Function | de |
dc.subject.eng | Co-Chaperone | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0028-87C2-D-8 | |
dc.affiliation.institute | Medizinische Fakultät | de |
dc.subject.gokfull | Neurologie - Allgemein- und Gesamtdarstellungen (PPN619876247) | de |
dc.subject.gokfull | Methoden und Techniken in der Medizin (PPN619875143) | de |
dc.subject.gokfull | Onkologie (PPN619875895) | de |
dc.subject.gokfull | Neurochirurgie (PPN619876271) | de |
dc.description.embargoed | 2016-08-08 | |
dc.identifier.ppn | 863193579 | |