Overexpression of Aurora-A contributes to malignant development of human esophageal squamous cell carcinoma

Clin Cancer Res. 2004 Nov 1;10(21):7304-10. doi: 10.1158/1078-0432.CCR-04-0806.

Abstract

Purpose: Aurora-A/STK15/BTAK, a centrosome-associated oncogenic protein, is implicated in the control of mitosis. Overexpression of Aurora-A has been shown to result in chromosomal aberration and genomic instability. Multiple lines of evidence indicate that Aurora-A induces cell malignant transformation. In the current study, we are interested in investigating the expression of Aurora-A in human esophageal squamous cell carcinoma (ESCC) and characterizing the association of Aurora-A with ESCCmalignant progression.

Experimental design: Aurora-A protein expression was examined in 84 ESCC tissues and 81 paired normal adjacent tissues by either immunohistochemistry or Western blot analysis. In addition, a gene-knockdown small interfering RNA technique was used in ESCC cells to investigate whether Aurora-A contributes to the ability of a tumor to grow invasively.

Results: The amount of Aurora-A protein in ESCC was considerably higher than that in normal adjacent tissues. Overexpression of Aurora-A was observed in 57 of 84 (67.5%) ESCC samples. In contrast, <2% of normal adjacent tissue displayed high expression of Aurora-A. Interestingly, overexpression of Aurora-A seemed to correlate with the invasive malignancy of ESCC. Disruption of endogenous Aurora-A using small interfering RNA technique substantially suppressed cell migrating ability.

Conclusion: The findings presented in this report show that Aurora-A expression is elevated in human esophageal squamous cell carcinoma and is possibly associated with tumor invasion, indicating that overexpression of Aurora-A may contribute to ESCC occurrence and progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A
  • Aurora Kinases
  • Blotting, Western
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Movement
  • Centrosome / ultrastructure
  • Disease Progression
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Esophagus / pathology
  • Humans
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Protein Kinases / biosynthesis*
  • Protein Kinases / physiology*
  • Protein Serine-Threonine Kinases
  • RNA, Small Interfering / metabolism
  • Time Factors
  • Xenopus Proteins

Substances

  • Cell Cycle Proteins
  • RNA, Small Interfering
  • Xenopus Proteins
  • Protein Kinases
  • AURKA protein, Xenopus
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases