PARP-1 protein expression in glioblastoma multiforme
Open accessAbstract
One of the most common type of primary brain tumors in adults is the glioblastoma multiforme (GBM) (World Health Organization grade IV astrocytoma). It is the most common malignant and aggressive form of glioma and it is among the most lethal ones. Poly (ADP-ribose) polymerase 1 (PARP-1) gene, located to 1q42, plays an important role for the efficient maintenance of genome integrity. PARP-1 protein is required for the apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. PARP-1 is proteolytically cleaved at the onset of apoptosis by caspase-3. Microarray analysis of PARP-1 gene expression in more than 8,000 samples revealed that PARP-1 is more highly expressed in several types of cancer compared with the equivalent normal tissues. Overall, the most differences in PARP-1 gene expression have been observed in breast, ovarian, endometrial, lung, and skin cancers, and non-Hodgkin's lymphoma. We evaluated the expression of PARP-1 protein in normal brain tissues and primary GBM by immunohistochemistry. Positive nuclear PARP-1 staining was found in all samples with GBM, but not in normal neurons from controls (n=4) and GBM patients (n=27). No cytoplasmic staining was observed in any sample. In conclusion, PARP-1 gene is expressed in GBM. This finding may be envisioned as an attempt to trigger apoptosis in this tumor, as well as in many other malignancies. The presence of the protein exclusively at the nucleus further support the function played by this gene in genome integrity maintenance and apoptosis. Finally, PARP-1 staining may be used as GBM cell marker.
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GOF mut-p53 has been shown to abnormally regulate a multitude of genes that play critical roles in glioblastoma pathogenesis, including CD95/Fas/Apo1, PARP, PTEN, and more.
“Furthermore, GOF mut-p53 has been shown to abnormally regulate a multitude of genes that play critical roles in GBM pathogenesis, but have not been analyzed in the context of GBM. This includes CD95/Fas/Apo1, PARP, PTEN, and more [63,94,95,96,97,98].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [63]
The Discussion (page not available in our copy) reports PARP-1 protein in GBM cells and suggests it may play a role in the tumor. It does not show that gain-of-function mutant p53 regulates PARP-1 or the other listed genes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIncreased expression of GOF mut-p53 is due to disruption of the MDM2/p53 negative feedback loop.
“Increased expression of GOF mut-p53 is due to the disruption of the MDM2/p53 negative feedback loop.”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [63]
The Introduction and Discussion discuss PARP-1 expression and function, not mutant p53. Searches for the MDM2/p53 negative feedback loop and gain-of-function mutant p53 found no passage addressing the claimed mechanism; page numbers were not provided in our copy. (LLM, conf=0.76)
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- Authors
- Galia, A., Calogero, A. E., Condorelli, R., Fraggetta, F., La Corte, A., Ridolfo, F., Bosco, P., Castiglione, R., & Salemi, M.
- Affiliations
- Ospedale Cannizzaro (IT)
- University of Catania (IT)
- University of Milan (IT)
- Oasi Maria SS (IT)
- Corresponding author
- Calogero, A.E.
- Venue
- European Journal of Histochemistry
- Publisher
- PAGEPress Publications
- Published
- 2012-02-27
- Volume
- 56
- Issue
- 1
- Pages
- 9
- ISSN
- 1121-760X (ISSN-L)
- 2038-8306
- PMC
- PMC3352138
- OpenAlex
- W2153172623
- Cited by
- 145
- References
- 28
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 14 · 2023: 4 · 2022: 17 · 2021: 9 · 2020: 16 · 2019: 7 · 2018: 6 · 2017: 17 · 2016: 10 · 2015: 12 · 2014: 7 · 2013: 5 · 2012: 6
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- European Journal of Histochemistry (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- PARP1, glioblastoma, protein expression, apoptosis, genome stability, caspase-3, apoptosis-inducing factor, nuclear localization, tumor markers, brain tumors
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Adult, Aged, Brain, Brain Neoplasms, Cell Nucleus, Female, Glioblastoma, Humans, Male, Middle Aged, Neoplasm Proteins, Nerve Tissue Proteins, Poly(ADP-ribose) Polymerases, Biomarkers, Tumor, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Apoptosis, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
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