Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice

Cancer Cell. 2007 Feb;11(2):161-73. doi: 10.1016/j.ccr.2006.11.025.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Aurora Kinase A
  • Aurora Kinases
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cells, Cultured
  • Down-Regulation
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Deletion
  • Gene Dosage
  • Gene Expression Profiling
  • Genomic Instability
  • Heterozygote
  • Lymphoma / genetics
  • Lymphoma / metabolism*
  • Lymphoma / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Microarray Analysis
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / metabolism*
  • Neoplasms, Radiation-Induced / pathology
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Survival Rate
  • Thymus Neoplasms / genetics
  • Thymus Neoplasms / metabolism*
  • Thymus Neoplasms / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*
  • Whole-Body Irradiation

Substances

  • Tumor Suppressor Protein p53
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases