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. 2010 Jul;140(1):225-32.
doi: 10.1016/j.jtcvs.2009.11.038. Epub 2010 Mar 16.

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

Elizabeth Chang  1 , James Donahue, Anna Smith, John Hornick, Jaladanki N Rao, Jian-Ying Wang, Richard J Battafarano
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Free article

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

Elizabeth Chang et al. J Thorac Cardiovasc Surg. 2010 Jul.
Free 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.

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