Wild-type p53 induces apoptosis in a Burkitt lymphoma (BL) line that carries mutant p53.
All Burkitt lymphoma (BL) biopsies and cell lines carry a c-myc/Ig translocation. The resulting constitutive activation of c-myc is regarded as an essential factor for the progressive growth of the tumor cells. At least 60% of BL cell lines carry a mutated p53 gene as well. It has been shown that the growth of mutant p53 carrying tumor cells could be inhibited by the introduction of wild-type p53. In order to examine whether this also applies to the presumably 'myc-driven' BL cell, we have transfected the Epstein-Barr virus (EBV) negative BL41 cell line with a temperature sensitive p53 mutant (p53-Val135) that expresses p53 with a largely mutant conformation at 37.5 degrees C and mostly wild-type conformation at 32 degrees C. At 37.5 degrees C, the p53-Val135 transfected cells behaved like the parental or neo transfected control cells. However, expression of exogenous wild-type p53 at 32 degrees C resulted in a rapid reduction of the number of viable cells while the parental and neo control cells remained unaffected. Cell death was due to apoptosis as shown by chromatin and nuclear condensation and specific DNA fragmentation. The first signs of apoptosis were evident after 10 h at 32 degrees C and after 3 days 90-100% of the cells had undergone apoptosis. These findings indicate an incompatibility between expression of wild-type p53 and progressive growth of BL cells if their neoplastic development has included a p53 mutation. The question whether apoptosis was induced in by the wild-type protein per se or by the contradictory signals of a constitutively activated c-myc and wild-type p53 needs further investigation.
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
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T
Ramqvist
K P
KP
Magnusson
Y
Y
Wang
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L
Szekely
G
G
Klein
K G
KG
Wiman
D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001706:Biopsy; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division; D002883:Chromosomes, Human, Pair 14; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000235:genetics; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D009838:Oligodeoxyribonucleotides