PMID- 10585266
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20151119
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 253
IP  - 2
DP  - 1999 Dec 15
TI  - Accumulation of mutant p53(V143A) modulates the growth, clonogenicity, and 
      radiochemosensitivity of malignant glioma cells independent of endogenous p53 
      status.
PG  - 432-9
AB  - 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 p53(V143A) in five human malignant glioma cell lines 
      with different genetic and functional p53 status. Accumulation of p53(V143A) 
      modulated proliferation in three and clonogenicity in four of five cell lines 
      without a clear pattern with regard to their endogenous p53 status. p53(V143A) 
      inhibited the camptothecin-induced accumulation of p21(WAF1/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 p53(V143A). 
      Irradiation induced a moderate G2/M arrest in all cell lines, irrespective of the 
      p53 status, that was unaffected by p53(V143A). 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 p53(V143A)-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.
CI  - Copyright 1999 Academic Press.
FAU - Bartussek, C
AU  - Bartussek C
AD  - Department of Neurology, University of Tubingen, Tubingen, 72076, Germany.
FAU - Naumann, U
AU  - Naumann U
FAU - Weller, M
AU  - Weller M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 5J49Q6B70F (Vincristine)
RN  - 7M7YKX2N15 (Topotecan)
RN  - 957E6438QA (Teniposide)
RN  - P88XT4IS4D (Paclitaxel)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U68WG3173Y (Carmustine)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Antineoplastic Agents, Alkylating/pharmacology
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - *Brain Neoplasms
MH  - Camptothecin/pharmacology
MH  - Carmustine/pharmacology
MH  - Cell Death/drug effects/radiation effects
MH  - Cell Division/physiology
MH  - Cisplatin/pharmacology
MH  - Clone Cells/physiology
MH  - Combined Modality Therapy
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects/radiation effects
MH  - Genes, Dominant
MH  - *Glioma
MH  - Humans
MH  - In Vitro Techniques
MH  - Paclitaxel/pharmacology
MH  - *Point Mutation
MH  - Radiotherapy
MH  - Teniposide/pharmacology
MH  - Topotecan/pharmacology
MH  - Tumor Cells, Cultured/cytology/drug effects/radiation effects
MH  - Tumor Suppressor Protein p53/*genetics/*metabolism
MH  - Vincristine/pharmacology
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - S0014-4827(99)94654-2 [pii]
AID - 10.1006/excr.1999.4654 [doi]
PST - ppublish
SO  - Exp Cell Res. 1999 Dec 15;253(2):432-9. doi: 10.1006/excr.1999.4654.