Kraus, Alison and Gross, Markus W. and Knuechel, Ruth and Muenkel, Kristin and Neff, Frauke and Schlegel, Juergen (2000) Aberrant p21 regulation in radioresistant primary glioblastoma multiforme cells bearing wild-type p53. JOURNAL OF NEUROSURGERY, 93 (5). pp. 863-872. ISSN 0022-3085
Full text not available from this repository. (Request a copy)Abstract
Object. A clearer understanding of the cellular mechanisms involved in the response to ionizing radiation is pivotal to the development of new therapeutic strategies for glioblastoma multiforme (GBM). To gain insight into dynamic functional aspects of cell cycle regulation and the control of apoptosis in GBMs, the authors investigated the molecular changes induced by ionizing radiation in genetically characterized primary GBMs in vitro compared with secondary GBMs, Grades II and III gliomas, and three GEM cell lines. Methods. Irradiation of primary GBMs bearing wild-type (wt) p53 invariably fails to invoke the G(1) checkpoint and apoptosis in vitro. In approximately half of these primary GBMs a defect lies at or above the level of p53 because transcriptional activation of p21 and bar after irradiation does not occur. The failure of a p21 response to irradiation is invariably accompanied by overexpression of pal mRNA under nonirradiated conditions. In all remaining primary GBMs transcriptional activation of p21 after irradiation does occur, suggesting that a defect downstream from p21 prevents G(1) arrest. Conclusions. These results show that the G(1) checkpoint and the p53 pathway are dysfunctional in primary GBMs in vitro, despite the presence of an intact p53 gene. The data also suggest that primary GBMs may be divided into two categories on the basis of their p21 response to irradiation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN BRAIN-TUMORS; GENETIC ALTERATIONS; HUMAN FIBROBLASTS; EXPRESSION; APOPTOSIS; WAF1/CIP1; PROTEIN; GROWTH; LINES; RADIOSENSITIVITY; glioblastoma multiforme; radioresistance; p21; p53 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Mar 2022 07:13 |
| Last Modified: | 21 Mar 2022 07:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42101 |
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