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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

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

Author

  • Y Wang
  • T Ramqvist
  • L Szekely
  • H Axelson
  • G Klein
  • K G Wiman

Summary, in English

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.

Department/s

  • Division of Translational Cancer Research

Publishing year

1993-06

Language

English

Pages

73-467

Publication/Series

Cell Growth & Differentiation

Volume

4

Issue

6

Document type

Journal article

Publisher

American Association for Cancer Research

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1044-9523