Aurora-A transcriptional silencing and vincristine treatment show a synergistic effect in human tumor cells

Oncol Res. 2008;17(3):115-25. doi: 10.3727/096504008785055521.

Abstract

Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G2/M cell cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide-, and paclitaxel-induced apoptosis. Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of human colon cancer. Aneuploidy was also observed after Aurora-A ectopic overexpression in colon cancer cells with MIN phenotype. Silencing of Aurora-A by RNA interference in tumor cell lines triggered arrest of the cell cycle associated to apoptosis/ mitotic catastrophe. Finally, Aurora-A transcriptional silencing seems to confer cancer cells a greater sensitivity to chemotherapy by vincristine, indicating Aurora-A as a possible gene target in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Apoptosis / drug effects*
  • Aurora Kinases
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Centrosome / chemistry
  • Centrosome / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / therapeutic use
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transcription, Genetic
  • Transfection
  • Vincristine / administration & dosage

Substances

  • Antineoplastic Agents, Phytogenic
  • RNA, Small Interfering
  • Vincristine
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases