Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis

Oncogene. 2005 Feb 3;24(6):1122-7. doi: 10.1038/sj.onc.1208293.

Abstract

Aurora kinases are known to play a key role in maintaining mitotic fidelity, and overexpression of aurora kinases has been noted in various tumors. Overexpression of aurora kinase activity is thought to promote cancer development through a loss of centrosome or chromosome number integrity. Here we observed augmentation of G12V-mutated HRAS-induced neoplastic transformation in BALB/c 3T3 A31-1-1 cells transfected with Aurora-A. Aurora-A-short hairpin RNA (shRNA) experiments showed that the expression level of Aurora-A determines susceptibility to transformation. Aurora-A gene amplification was noted in human patients with tongue or gingival squamous carcinoma (4/11). Amplification was observed even in pathologically normal epithelial tissue taken at sites distant from the tumors in two patients with tongue cancer. However, overexpression of Aurora-A mRNA was observed only within the tumors of all patients examined (11/11). Our data indicate that Aurora-A gene amplification and overexpression play a role in human carcinogenesis, largely due to the effect of Aurora-A on oncogenic cell growth, rather than a loss of maintenance of centrosomal or chromosomal integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Cycle Proteins
  • Cell Transformation, Neoplastic / genetics*
  • Gene Amplification*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease
  • Gingival Neoplasms / genetics*
  • Gingival Neoplasms / physiopathology*
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Genetic
  • Protein Kinases / biosynthesis*
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / physiopathology*
  • Xenopus Proteins
  • ras Proteins / genetics
  • ras Proteins / pharmacology

Substances

  • Cell Cycle Proteins
  • RNA, Messenger
  • Xenopus Proteins
  • Protein Kinases
  • AURKA protein, Xenopus
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • ras Proteins