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Reconstitution of wild-type p53 expression triggers apoptosis in a p53-negative v-myc retrovirus-induced T-cell lymphoma line

Wang, Y; Ramqvist, T; Szekely, L; Axelson, H LU ; Klein, G and Wiman, K G (1993) In Cell Growth & Differentiation 4(6). p.73-467
Abstract

Inactivation or mutation of the p53 tumor suppressor gene has been observed in a wide variety of human and murine tumors. We have found that a v-myc retrovirus (J3)-induced T-cell lymphoma line (J3D) has lost one of its p53 alleles, whereas the other has become inactivated due to the insertion of a Moloney murine leukemia provirus in intron 4 with an opposite transcriptional orientation. No p53 protein could be detected by immunoprecipitation with monoclonal anti-p53 antibodies. We have transfected this line with the temperature-sensitive murine Val135 construct that is expressed as mutant p53 at 37 degrees C and largely wild-type p53 at 32 degrees C. There was no difference in the number of viable cells among the p53 transfectants, the... (More)

Inactivation or mutation of the p53 tumor suppressor gene has been observed in a wide variety of human and murine tumors. We have found that a v-myc retrovirus (J3)-induced T-cell lymphoma line (J3D) has lost one of its p53 alleles, whereas the other has become inactivated due to the insertion of a Moloney murine leukemia provirus in intron 4 with an opposite transcriptional orientation. No p53 protein could be detected by immunoprecipitation with monoclonal anti-p53 antibodies. We have transfected this line with the temperature-sensitive murine Val135 construct that is expressed as mutant p53 at 37 degrees C and largely wild-type p53 at 32 degrees C. There was no difference in the number of viable cells among the p53 transfectants, the parental cells, and neomycin vector-transfected control cells at 37 degrees C. Following a temperature shift to 32 degrees C, the p53 transfectants rapidly lost viability, and 95-100% of the cells were dead by 3 days, whereas the control cells remained unaffected. Examination of DNA isolated from p53-transfected cells grown at 32 degrees C revealed nucleosomal fragmentation, indicating cell death by apoptosis. It is suggested that apoptosis is triggered by contradictory signaling. Constitutively expressed v-myc can stimulate cell proliferation, whereas expression of wild-type p53 in cells that have lost endogenous p53 expression in the course of their neoplastic development may suppress growth.

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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
Alleles, Animals, Apoptosis, Cell Transformation, Viral, Gene Deletion, Gene Expression Regulation, Neoplastic, Genes, myc, Genes, p53, Lymphoma, T-Cell, Mice, Moloney murine leukemia virus, Mutagenesis, Insertional, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Virus Integration
in
Cell Growth & Differentiation
volume
4
issue
6
pages
7 pages
publisher
American Association for Cancer Research
external identifiers
  • Scopus:0027615656
ISSN
1044-9523
language
English
LU publication?
yes
id
7145babf-974e-4383-8d64-49e43f953ce8
date added to LUP
2016-08-09 09:19:56
date last changed
2016-11-14 09:42:58
@misc{7145babf-974e-4383-8d64-49e43f953ce8,
  abstract     = {<p>Inactivation or mutation of the p53 tumor suppressor gene has been observed in a wide variety of human and murine tumors. We have found that a v-myc retrovirus (J3)-induced T-cell lymphoma line (J3D) has lost one of its p53 alleles, whereas the other has become inactivated due to the insertion of a Moloney murine leukemia provirus in intron 4 with an opposite transcriptional orientation. No p53 protein could be detected by immunoprecipitation with monoclonal anti-p53 antibodies. We have transfected this line with the temperature-sensitive murine Val135 construct that is expressed as mutant p53 at 37 degrees C and largely wild-type p53 at 32 degrees C. There was no difference in the number of viable cells among the p53 transfectants, the parental cells, and neomycin vector-transfected control cells at 37 degrees C. Following a temperature shift to 32 degrees C, the p53 transfectants rapidly lost viability, and 95-100% of the cells were dead by 3 days, whereas the control cells remained unaffected. Examination of DNA isolated from p53-transfected cells grown at 32 degrees C revealed nucleosomal fragmentation, indicating cell death by apoptosis. It is suggested that apoptosis is triggered by contradictory signaling. Constitutively expressed v-myc can stimulate cell proliferation, whereas expression of wild-type p53 in cells that have lost endogenous p53 expression in the course of their neoplastic development may suppress growth.</p>},
  author       = {Wang, Y and Ramqvist, T and Szekely, L and Axelson, H and Klein, G and Wiman, K G},
  issn         = {1044-9523},
  keyword      = {Alleles,Animals,Apoptosis,Cell Transformation, Viral,Gene Deletion,Gene Expression Regulation, Neoplastic,Genes, myc,Genes, p53,Lymphoma, T-Cell,Mice,Moloney murine leukemia virus,Mutagenesis, Insertional,Recombinant Fusion Proteins,Transfection,Tumor Cells, Cultured,Tumor Suppressor Protein p53,Virus Integration},
  language     = {eng},
  number       = {6},
  pages        = {73--467},
  publisher    = {ARRAY(0xaac0e10)},
  series       = {Cell Growth & Differentiation},
  title        = {Reconstitution of wild-type p53 expression triggers apoptosis in a p53-negative v-myc retrovirus-induced T-cell lymphoma line},
  volume       = {4},
  year         = {1993},
}