Article
Activating transcription factor 5 – a new therapeutic target for treatment of astrocytomas?
Search Medline for
Authors
-
Jonas Feldheim
- Neurochirurgische Klinik und Poliklinik, Universitätsklinikum Würzburg, Germany
-
Almuth F. Keßler
- Neurochirurgische Klinik und Poliklinik, Universitätsklinikum Würzburg, Germany
-
Carsten Hagemann
- Neurochirurgische Klinik und Poliklinik, Universitätsklinikum Würzburg, Germany
-
Thomas Linsenmann
- Neurochirurgische Klinik und Poliklinik, Universitätsklinikum Würzburg, Germany
-
Ralf-Ingo Ernestus
- Neurochirurgische Klinik und Poliklinik, Universitätsklinikum Würzburg, Germany
-
Mario Löhr
- Neurochirurgische Klinik und Poliklinik, Universitätsklinikum Würzburg, Germany
| Published: | June 8, 2016 |
|---|
Outline
Text
Objective: Activating transcription factor 5 (ATF5) is a widely expressed basic leucine zipper protein, that is known to suppress differentiation of neuroprogenitor cells into neurons or glia in the normal brain (NB) and has been reported to be overexpressed in glioblastoma (GBM). Since it has been shown that glioblastoma cells undergo p53-independent apoptotic cell death, when ATF5 expression or activity is lowered, it might serve as a novel therapeutic target. However, there are no data on ATF5 expression in low-grade astrocytomas (LGA) and recurrent GBM. The aim of our study was to investigate the ATF5-expression in astrocytomas of different WHO grades and varying biological behavior.
Method: ATF5-expression was measured on mRNA-level by quantitative PCR (qPCR) by extracting the RNA of frozen samples of GBM (n=15), LGA (n=12) and normal brain (NB, n=4). Aditionally, qPCR was performed on tumor samples of an independent panel of GBM of varying biological behavior, i.e. GBM, with local growth and local relapse (primary tumor (LP): n=26; relapse (LR): n=8), GBM with local growth and multifocal relapse (primary tumor (MRP): n=12; relapse (MRR): n=3) and GBM with a multifocal growth pattern (PM, n=9). Data were analyzed using unpaired two-sided t-test.
Results: In comparison to NB, ATF5 was nearly 12 times overexpressed in LGA (p=0.004), as well as in GBM (p<0.001). In addition, the subgroup-analysis showed a significant increase in LP (p=0.015), LR (p=0.041), MRP (p=0.018) and PM (p=0.012), whereas there was no difference between primary tumor and local (p=0.572)/multifocal relapse (p=0.577). Primary tumors LP, MRP, PM showed a similar expression (p>0.05), independent of local/multifocal growth.
Conclusions: In comparison to NB, ATF5 is overexpressed not only in GBM, but also in LGA and independently of tumor growth patterns. As previously reported, inhibition of ATF5 might lead to selective death of glioma cells, but not of non-tumor cells. Therefore, in contrast to different therapeutically and prognostically relevant factors as EGFR-amplification or MGMT-promoter methylation status, ATF5 might even serve as an ubiquitous potential therapeutic target in astrocytic tumors, independently of WHO grading or growth pattern.
