Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line

Cell Res. 2006 Apr;16(4):356-66. doi: 10.1038/sj.cr.7310046.

Abstract

Aurora-A kinase, a serine/threonine protein kinase, is a potential oncogene. Amplification and overexpression of Aurora-A have been found in several types of human tumors, including esophageal squamous cell carcinoma (ESCC). It has been demonstrated that cells overexpressing Aurora-A are more resistant to cisplatin-induced apoptosis. However, the molecular mechanisms mediating these effects remain largely unknown. In this report, we showed that overexpression of Aurora-A through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin- or UV irradiation-induced apoptosis. Cleavages of caspase-3 and poly (ADP-ribose) polymerase (PARP) in Aurora-A overexpressing cells were substantially reduced after cisplatin or UV treatment. Furthermore, we found that silencing of endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells. In parallel, overexpression of Aurora-A potently upregulated the expression of Bcl-2. Moreover, the knockdown of Bcl-2 by siRNA abrogated the Aurora-A's effect on inhibiting apoptosis. Taken together, these data provide evidence that Aurora-A overexpression promoting cell proliferation and inhibiting apoptosis, suggesting a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of ESCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Apoptosis Regulatory Proteins / genetics*
  • Aurora Kinases
  • Caspase 3
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cisplatin / antagonists & inhibitors
  • Esophageal Neoplasms / genetics*
  • Humans
  • Neoplasms, Squamous Cell / genetics*
  • Neoplasms, Squamous Cell / metabolism
  • Neoplastic Stem Cells
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA Interference / drug effects
  • RNA Interference / radiation effects
  • RNA, Small Interfering / drug effects
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / radiation effects
  • Radiation Tolerance / genetics
  • Transfection
  • Ultraviolet Rays

Substances

  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Poly(ADP-ribose) Polymerases
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cisplatin