Abstract
The Aurora-A kinase gene is amplified in a subset of human tumors and in radiation-induced lymphomas from p53 heterozygous mice. Normal tissues from p53-/- mice have increased Aurora-A protein levels, but lymphomas from these mice exhibit heterozygous deletions of Aurora-A and/or reduced protein expression. A similar correlation between low p53 levels and Aurora-A gene deletions and expression is found in human breast cancer cell lines. In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status. These data have implications for the design of approaches to targeted cancer therapy involving the crosstalk between Aurora-A kinase and p53 pathways.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Apoptosis
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Aurora Kinase A
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Aurora Kinases
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cells, Cultured
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Down-Regulation
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Female
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Deletion
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Gene Dosage
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Gene Expression Profiling
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Genomic Instability
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Heterozygote
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Lymphoma / genetics
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Lymphoma / metabolism*
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Lymphoma / pathology
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Male
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Mice
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Mice, Knockout
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Microarray Analysis
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Neoplasms, Radiation-Induced / genetics
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Neoplasms, Radiation-Induced / metabolism*
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Neoplasms, Radiation-Induced / pathology
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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Survival Rate
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Thymus Neoplasms / genetics
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Thymus Neoplasms / metabolism*
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Thymus Neoplasms / pathology
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology*
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Whole-Body Irradiation
Substances
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Tumor Suppressor Protein p53
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Aurka protein, mouse
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Aurora Kinase A
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Aurora Kinases
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Protein Serine-Threonine Kinases