A mutant p53 antagonizes the deregulated c-myc-mediated enhancement of apoptosis and decrease in leukemogenicity.

J Lotem; L Sachs

doi:10.1073/pnas.92.21.9672

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A mutant p53 antagonizes the deregulated c-myc-mediated enhancement of apoptosis and decrease in leukemogenicity.

J Lotem·L Sachs

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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.

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Animals Apoptosis Blotting, Northern Cell Division Clone Cells DNA Damage Gene Expression Regulation, Leukemic Leukemia, Experimental Leukemia, Myeloid Mice Mutation Proto-Oncogene Proteins c-myc Survival Analysis Transfection Tumor Cells, Cultured Tumor Suppressor Protein p53 Journal Article Research Support, Non-U.S. Gov't

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J Lotem, L Sachs. 1995-10-10. A mutant p53 antagonizes the deregulated c-myc-mediated enhancement of apoptosis and decrease in leukemogenicity.. https://doi.org/10.1073/pnas.92.21.9672

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