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Antiproliferative effect of Aurora kinase targeting in mesothelioma

Stefania Crispi1, Claudia Fagliarone, Annamaria Biroccio

  • 1Gene Expression Core-Human Molecular Genetics Laboratory, Institute of Genetics and Biophysics, CNR, Naples, Italy.

Lung Cancer (Amsterdam, Netherlands)
|April 8, 2010
PubMed

Insights

Aurora kinases A and B are overexpressed in mesothelioma, a cancer of the lung lining. Inhibiting these Aurora kinases with ZM447439 suppressed mesothelioma cell growth, suggesting a therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Aurora kinases are serine/threonine kinases crucial for mitosis.
  • Dysregulation of Aurora kinases is implicated in various cancers, making them potential therapeutic targets.
  • Mesothelioma is a rare but aggressive cancer with limited treatment options.

Purpose of the Study:

  • To investigate the expression of Aurora kinases A and B and related genes in human mesothelioma.
  • To evaluate the efficacy of the Aurora kinase inhibitor ZM447439 on mesothelioma cell lines.
  • To determine the mechanism of ZM447439-induced growth inhibition.

Main Methods:

  • Quantitative analysis of Aurora kinase A and B and related gene expression in mesothelioma tissues and cell lines.
  • Treatment of five mesothelioma cell lines with ZM447439.
  • Assessment of cell viability and proliferation.
  • Measurement of Histone H3 phosphorylation levels.

Main Results:

  • Overexpression of Aurora kinase A and related genes was observed in human mesothelioma tissues.
  • Aurora kinases A and B were overexpressed in all tested mesothelioma cell lines.
  • ZM447439 significantly inhibited cell growth across all mesothelioma cell lines.
  • Inhibition of cell growth by ZM447439 was associated with reduced Histone H3 phosphorylation.

Conclusions:

  • Aurora kinase A and B play a significant role in mesothelioma development and progression.
  • Targeting Aurora kinases with inhibitors like ZM447439 shows therapeutic potential for mesothelioma.
  • Further investigation into Aurora kinase inhibitors as a mesothelioma treatment is warranted.

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