Proceedings of the National Academy of Sciences - PNAS, 2009-03, Vol.106 (10), p.3964-3969
2009
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- Autor(en) / Beteiligte
- Titel
- A Panel of Isogenic Human Cancer Cells Suggests a Therapeutic Approach for Cancers with Inactivated P53
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2009-03, Vol.106 (10), p.3964-3969
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Through targeted homologous recombination, we developed a panel of matched colorectal cancer cell lines that differ only with respect to their endogenous TP53 status. We then used these lines to define the genes whose expression was altered after DNA damage induced by ionizing radiation. Transcriptome analyses revealed a consistent upregulation of polo-like kinase 1 (PLK1) as well as other genes controlling the G₂/M transition in the cells whose TP53 genes were inactivated compared with those with WT TP53 genes. This led to the hypothesis that the viability of stressed cells without WT TP53 depended on PLK1. This hypothesis was validated by demonstrating that stressed cancer cells without WT TP53 alleles were highly sensitive to PLK1 inhibitors, both in vivo and in vitro.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0813333106Titel-ID: cdi_crossref_primary_10_1073_pnas_0813333106
- Format
- –
- Schlagworte
- Alleles, Animals, Antineoplastic Agents - pharmacology, Biological Sciences, Cancer, Cell cycle, Cell Line, Tumor, Cell lines, Cells, Colorectal cancer, Cyclin-Dependent Kinase Inhibitor p21 - metabolism, DNA damage, G1 Phase - drug effects, Gene expression, Gene Expression Profiling, Gene Targeting, Genes, Genetic mutation, Genotype, HCT116 cells, Humans, Imidazoles - metabolism, Kinases, Medical treatment, Mice, Neoplasms - pathology, Neoplasms - therapy, p53 genes, Piperazines - metabolism, Pteridines - pharmacology, Transcription, Genetic - drug effects, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumors, Xenograft Model Antitumor Assays