Accumulation of wild-type p53 in astrocytomas is associated with increased p21 expression |
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Authors: | Yasuhiro Ono T Tamiya Tomotsugu Ichikawa Kengo Matsumoto Tomohisa Furuta Takashi Ohmoto Kosuke Akiyama Shuji Seki Keisuke Ueki David N Louis |
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Institution: | (1) Department of Neurological Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700, Japan Tel.: 81-86-235-7336; Fax: 81-86-227-0191; e-mail: ttamiya@med.okayama-u.ac.jp, JP;(2) Department of Molecular Biology, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama, Japan, JP;(3) Molecular Neuro-Oncology Laboratory, Department of Pathology and Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston, Mass., USA, US |
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Abstract: | Approximately one quarter of human astrocytomas show immunohistochemical positivity for p53 protein but lack p53 gene mutations, which could reflect either an accumulation of wild-type p53 protein or an inadequate sensitivity of mutation
detection. Since wild-type p53 up-regulates p21 expression, increased p21 expression in those astrocytomas with p53 accumulation
in the absence of mutations would argue that the protein was wild type in these tumors. We therefore compared p21 expression
with p53 gene and protein status in 48 primary human astrocytomas. Single-strand conformation polymorphism analysis and direct sequencing
of the p53 gene showed mutations in 11 tumors (22.9%), while immunohistochemistry revealed positive staining in 19 cases (39.6%). Those
tumors with p53 immunopositivity in the absence of p53 mutation had significantly increased p21 expression when compared to
either mutant p53 or p53-immunonegative cases. Neither p53 nor p21 status correlated with proliferation indices, as assessed by Ki-67 immunohistochemistry.
These results support the hypotheses that functionally wild-type p53 accumulates in some astrocytomas, and that alternative
cell cycle checkpoints (such as the p16 pathway) may be more important than p21 in regulating proliferation in astrocytomas.
Received: 11 October 1996 / Revised, accepted: 17 January 1997 |
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Keywords: | p21 p53 Astrocytoma Single-strand conformation polymorphism Immunohistochemistry |
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