Increased levels of p21WAF1/Cip1 in human brain tumors.

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.