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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adenoviridae, Animals, Blotting, Western, Cell Division, Cell Line, Cell Line, Transformed, Cell Transformation, Neoplastic, Chloramphenicol O-Acetyltransferase, Cysteine Endopeptidases, DNA Damage, DNA, Recombinant, Doxorubicin, Gene Expression Regulation, Neoplastic, Gene Transfer Techniques, Genes, Reporter, Genes, ras, Genetic Vectors, Leupeptins, Mice, Mice, Inbred C3H, Multienzyme Complexes, Muscles, Neoplasm Proteins, Nuclear Proteins, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, beta-Galactosidase.
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Is exogenous wt-p53 protein active in transformed cells but not in their non-transformed counterparts : implications for cancer gene therapy without tumor targeting? Context: Expression of exogenous wild-type p53 (wt-p53) protein in tumor cells can suppress the transformed phenotype whereas it does not apparently induce detrimental effects in non-transformed cells. This observation may provide a molecular basis for p53-mediated gene therapy of p53-sensitive cancers without the need for tumor targeting. To understand the molecular mechanisms responsible for this different behavior in tumor versus normal cells, biochemical and functional analyses of exogenous wt-p53 protein were performed on non-transformed C2C12 myoblasts and their transformed counterparts, the C2-ras cells. The exogenous wt-p53 protein, which induced persistent growth arrest only in transformed C2-ras cells, was shown to be significantly more stable in transformed than in non-transformed cells. This different stability was due to different p53 proteolytic degradation. Moreover, constitutively, exogenous wt-p53 protein was found to be transcriptionally active only in C2-ras cells but it could also be activated in C2C12 cells by genotoxic damage.
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Non-transformed C2C12 cells present regulatory system(s) which control the expression and the activity of exogenously expressed wt-p53 protein probably through degradation and maintenance in a latent form. This regulatory system is lost/inactivated upon transformation. Final Decision: yes