title: A mutant p53 antagonizes the deregulated c-myc-mediated enhancement of apoptosis and decrease in leukemogenicity.
abstract: Myeloid leukemic M1 cells that do not express p53 and transfected M1 clones that constitutively express the [Val135]p53 mutant or deregulated c-myc or coexpressing both genes grew autonomously in culture with a similar growth rate and cloning efficiency. Expression of deregulated c-myc in M1 leukemic cells enhanced susceptibility to induction of apoptotic cell death and resulted in a reduced leukemogenicity when injected into isologous mice. Expression of the [Val135]p53 mutant did not change cell susceptibility to induction of apoptosis or leukemogenicity, but expression of this mutant p53 suppressed the effects of deregulated c-myc on these properties. The results indicate that the [Val135]p53 mutant can show a gain of function for susceptibility to apoptosis and leukemogenicity in leukemic cells with deregulated c-myc and, thus, enhance tumor development.
authors.affiliation: Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Lotem
authors.forename: L
authors.initials: L
authors.lastname: Sachs
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015152:Blotting, Northern; D002455:Cell Division; D002999:Clone Cells; D004249:DNA Damage; D015973:Gene Expression Regulation, Leukemic; D007942:Leukemia, Experimental; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53