Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells

J Neurooncol. 2012 May;107(3):517-26. doi: 10.1007/s11060-011-0795-y. Epub 2012 Jan 15.

Abstract

Atypical teratoid/rhabdoid tumors (ATRT) are rare, highly malignant, embryonal CNS tumors with a poor prognosis. Therapy relies on highly toxic chemotherapy and radiotherapy. To improve outcomes and decrease morbidity, more targeted therapy is required. Gene expression analysis revealed elevated expression of multiple kinases in ATRT tissues. Aurora Kinase A was one of the candidate kinases. The objective of this study was to evaluate the impact of Aurora Kinase A inhibition in ATRT cell lines. Our analysis revealed that inhibition of Aurora Kinase A induces cell death in ATRT cells and the small molecule inhibitor MLN 8237 sensitizes these cells to radiation. Furthermore, inhibition of Aurora Kinase A resulted in decreased activity of pro-proliferative signaling pathways. These data indicate that inhibition of Aurora Kinase A is a promising small molecule target for ATRT therapy.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Aurora Kinase A
  • Aurora Kinases
  • Azepines / pharmacology
  • Blotting, Western
  • Central Nervous System Neoplasms / enzymology*
  • Central Nervous System Neoplasms / genetics
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Profiling
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Pyrimidines / pharmacology
  • Radiation Tolerance / genetics*
  • Real-Time Polymerase Chain Reaction
  • Rhabdoid Tumor / enzymology*
  • Rhabdoid Tumor / genetics
  • Teratoma / enzymology*
  • Teratoma / genetics
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Azepines
  • Enzyme Inhibitors
  • MLN 8237
  • Pyrimidines
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases