Article
Role of co-chaperone BAG-1 in glioma
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Published: | June 2, 2015 |
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Objective: 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 little is known about BAG-1 in GBM.
Method: 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.
Conclusions: On the way to developing individualized 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 study, BAG-1 reduces GBM growth most likely by sensitizing towards apoptosis. The role of protein degradation mechanisms in GBM is poorly understood. This study provides first data on the impact of BAG-1 on autophagy and proteasomal function in GBM. Further work needs to be done in order to evaluate the role of BAG-1 in GBM diagnostics and therapy.