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Increased levels of p21WAF1/Cip1 in human brain tumors
1Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The cdk inhibitor p21WAF1/Cip1 (p21), which can be transcriptionally activated by p53, functions to block cell cycle progression. In this study, we analysed the expression of p21 in normal and reactive brain and in gliomas of various malignancy grades. Southern blotting showed no p21 gene deletion. Western blotting and immunohistochemical assay showed that the levels of p21 protein in normal and reactive brain tissue were very low; however, p21 was elevated in a majority of gliomas tested, regardless of their malignancy grades. In glioblastoma multiforme, marked elevation of p21 was observed in samples harboring either wild-type or mutant p53. But, in anaplastic astrocytomas, the level of p21 was not elevated in samples harboring mutant-type p53. Immunohistochemical staining of paraffin-embedded astrocytomas and glioblastomas showed that tumor cells and not contaminating normal cells were positive for p21. Therefore, overexpression of p21 appears to be an early event in the development of glial neoplasms and p53-dependent p21 expression appears to be tumor grade specific.
Insights
p21 protein overexpression is common in gliomas, regardless of grade. Its expression in anaplastic astrocytomas is linked to p53 status, suggesting it’s an early event in glial tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Neuroscience
Background:
- The cyclin-dependent kinase inhibitor p21WAF1/Cip1 (p21) is activated by p53 and inhibits cell cycle progression.
- Understanding p21 expression is crucial for comprehending glial tumor development.
Purpose of the Study:
- To analyze p21 expression in normal brain, reactive brain tissue, and gliomas of varying malignancy grades.
- To investigate the correlation between p21 expression, p53 status, and glioma grade.
Main Methods:
- Southern blotting to assess p21 gene deletion.
- Western blotting and immunohistochemistry to quantify p21 protein levels.
- Analysis of p53 wild-type and mutant status in tumor samples.
Main Results:
- No p21 gene deletions were detected.
- p21 protein levels were low in normal and reactive brain tissue but elevated in most gliomas.
- Glioblastoma multiforme showed elevated p21 regardless of p53 status.
- Anaplastic astrocytomas with mutant p53 did not show elevated p21.
- Immunohistochemistry confirmed p21 positivity in tumor cells, not contaminating normal cells.
Conclusions:
- p21 overexpression is an early event in glial neoplasm development.
- p53-dependent p21 expression is specific to tumor grade.
- p21 is a potential biomarker in glial tumor progression.