Loss of p53, rather than beta-catenin overexpression, induces survivin-mediated resistance to apoptosis in an esophageal cancer cell line

Academic Article

Abstract

  • Objective: Survivin, an important inhibitor of apoptosis, is overexpressed in esophageal cancer and negatively affects survival. The complex regulation of survivin transcription involves enhancement by beta-catenin and repression by p53. The purpose of this study is to test whether inhibition of beta-catenin or overexpression of p53 can decrease survivin expression and render esophageal cancer cells more susceptible to apoptosis. Methods: Studies were performed in normal human esophageal epithelial cells and the human esophageal cancer cell line TE7. Levels of beta-catenin, survivin, and p53 were measured by Western blot. Apoptosis was induced after treatment with camptothecin and measured by release of caspase 3 and morphologic criteria. The roles of survivin and beta-catenin in preventing apoptosis were tested by their silencing with specific small interfering RNA molecules. The effect of p53 overexpression on survivin promoter activity was measured using a survivin promoter-luciferase reporter construct and by real-time polymerase chain reaction measurement of survivin mRNA levels. Results: Both beta-catenin and survivin are overexpressed in TE7 cells, whereas p53 expression is negligible. TE7 cells demonstrate resistance to camptothecin-induced apoptosis (P < .01). This effect is significantly reduced by inhibition of survivin, but not of beta-catenin (P < .01). Overexpression of p53 in TE7 cells reduces survivin transcription and mRNA levels (P < .01), without reducing survivin protein levels. Conclusion: Survivin plays a critical role in TE7 cell resistance to camptothecin-induced apoptosis. This effect is not dependent on beta-catenin expression. Overexpression of p53 decreases survivin transcription but does not decrease levels of survivin protein, suggesting posttranscriptional control of survivin expression. © 2010 The American Association for Thoracic Surgery.
  • Authors

    Digital Object Identifier (doi)

    Pubmed Id

  • 15023870
  • Author List

  • Chang E; Donahue J; Smith A; Hornick J; Rao JN; Wang JY; Battafarano RJ
  • Start Page

  • 225
  • End Page

  • 232
  • Volume

  • 140
  • Issue

  • 1