Accumulation of Mutant p53 Modulates the Growth, Clonogenicity, and Radiochemosensitivity of Malignant Glioma Cells Independent of Endogenous p53 Status |
| |
Authors: | Cornelia Bartussek Ulrike Naumann Michael Weller |
| |
Affiliation: | Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of Tübingen, 72076, Tübingen, Germany |
| |
Abstract: | Alterations of the p53 gene have been attributed a major role in the development and resistance to therapy of several human cancers. Accumulation of p53 in tumor cells may result from mutations associated with prolonged half-life or from stabilization of wild-type p53 by different mechanisms. To address the role of p53 accumulation in the response of malignant glioma cells to radiochemotherapy, we expressed the p53 mutant p53V143A in five human malignant glioma cell lines with different genetic and functional p53 status. Accumulation of p53V143A modulated proliferation in three and clonogenicity in four of five cell lines without a clear pattern with regard to their endogenous p53 status. p53V143A inhibited the camptothecin-induced accumulation of p21WAF1/CIP1 in cell lines with p53 functional wild-type activity, but not in cell lines lacking p53 activity, consistent with a transdominant-negative effect of p53V143A. Irradiation induced a moderate G2/M arrest in all cell lines, irrespective of the p53 status, that was unaffected by p53V143A. Radiosensitivity as well as sensitivity to BCNU, teniposide (VM26), topotecan, vincristine, Taxol, and cisplatin both in cytotoxic cell death and in clonogenic cell death was unchanged in p53V143A-transfected cells with few exceptions. These data do not support the hypothesis that accumulation of mutant p53 is a major determinant of the response to adjuvant radiochemotherapy in human malignant glioma cells. |
| |
Keywords: | apoptosis chemotherapy glioma p21WAF1/CIP1 p53 radiotherapy |
本文献已被 ScienceDirect 等数据库收录! |
|