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Reconstitution of w...
Reconstitution of wild-type p53 expression triggers apoptosis in a p53-negative v-myc retrovirus-induced T-cell lymphoma line
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Wang, Y (författare)
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Ramqvist, T (författare)
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Szekely, L (författare)
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- Axelson, H (författare)
- Karolinska Institutet,Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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Klein, G (författare)
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Wiman, K G (författare)
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visa färre...
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(creator_code:org_t)
- 1993
- 1993
- Engelska 7 s.
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Ingår i: Cell Growth & Differentiation. - 1044-9523. ; 4:6, s. 73-467
- Relaterad länk:
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https://lup.lub.lu.s...
Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- 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
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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