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ID1 affects the efficacy of radiotherapy in glioblastoma through inhibition of DNA repair pathways.
- Source :
-
Medical oncology (Northwood, London, England) [Med Oncol] 2013 Mar; Vol. 30 (1), pp. 325. Date of Electronic Publication: 2013 Feb 03. - Publication Year :
- 2013
-
Abstract
- Glioblastoma multiforme (GBM) is characterized by poor therapeutic response and poor overall survival. It is crucial that more effective therapies be developed for the treatment of GBM. Inhibitor of DNA binding protein-1 (ID1) has been shown to maintain the self-renewal capacity of neural stem cells and might be involved in the therapeutic resistance of GBM. In the present study, we explored survival data from the The Cancer Genome Atalas database that were based on ID1 expression for patients diagnosed with primary GBMs. Interestingly, patients with high ID1 expression had better survival than patients with low ID1 expression, and a strong correlation was found between radiotherapy efficacy, ID1 expression, and overall survival. We further investigated the relationship between ID1 expression and the radiosensitivity of glioblastoma using glioblastoma cell lines. The clonogenic formation assay showed that U87 ID1-shRNA cells were much less sensitive to radiation. Moreover, both the results of the γH2AX foci staining assay and the comet assay further revealed that ID1 negatively regulates DNA repair processes by downregulating the expression of genes such as DNA ligase IV (LIG4) and ataxia-telangiectasia-mutated. Additionally, ID1 induces G2/M arrest in U87 cells. Taken together, these results suggest that ID1 may be a new prognostic marker for GBM and have important implications for the therapeutic strategies used to treat GBM patients.
- Subjects :
- Biomarkers, Tumor analysis
Biomarkers, Tumor genetics
Blotting, Western
Brain Neoplasms metabolism
Brain Neoplasms radiotherapy
Comet Assay
Fluorescent Antibody Technique
Glioblastoma metabolism
Glioblastoma radiotherapy
Humans
Inhibitor of Differentiation Protein 1 metabolism
Kaplan-Meier Estimate
Prognosis
Proportional Hazards Models
Real-Time Polymerase Chain Reaction
Brain Neoplasms genetics
DNA Repair genetics
Glioblastoma genetics
Inhibitor of Differentiation Protein 1 genetics
Radiation Tolerance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-131X
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Medical oncology (Northwood, London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 23377983
- Full Text :
- https://doi.org/10.1007/s12032-012-0325-6