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

Elizabeth Chang, James Donahue, Anna Smith, John Hornick, Jaladanki N. Rao, Jian Ying Wang, Richard J Battafarano

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)225-232
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume140
Issue number1
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

beta Catenin
Esophageal Neoplasms
Apoptosis
Cell Line
Camptothecin
Messenger RNA
Luciferases
Caspase 3
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Proteins
Western Blotting
Epithelial Cells
Survival

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Loss of p53, rather than beta-catenin overexpression, induces survivin-mediated resistance to apoptosis in an esophageal cancer cell line. / Chang, Elizabeth; Donahue, James; Smith, Anna; Hornick, John; Rao, Jaladanki N.; Wang, Jian Ying; Battafarano, Richard J.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 140, No. 1, 07.2010, p. 225-232.

Research output: Contribution to journalArticle

Chang, Elizabeth ; Donahue, James ; Smith, Anna ; Hornick, John ; Rao, Jaladanki N. ; Wang, Jian Ying ; Battafarano, Richard J. / Loss of p53, rather than beta-catenin overexpression, induces survivin-mediated resistance to apoptosis in an esophageal cancer cell line. In: Journal of Thoracic and Cardiovascular Surgery. 2010 ; Vol. 140, No. 1. pp. 225-232.
@article{97faa03d040f4d669a996f832469cc34,
title = "Loss of p53, rather than beta-catenin overexpression, induces survivin-mediated resistance to apoptosis in an esophageal cancer cell line",
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.",
author = "Elizabeth Chang and James Donahue and Anna Smith and John Hornick and Rao, {Jaladanki N.} and Wang, {Jian Ying} and Battafarano, {Richard J}",
year = "2010",
month = "7",
doi = "10.1016/j.jtcvs.2009.11.038",
language = "English (US)",
volume = "140",
pages = "225--232",
journal = "Journal of Thoracic and Cardiovascular Surgery",
issn = "0022-5223",
publisher = "Mosby Inc.",
number = "1",

}

TY - JOUR

T1 - Loss of p53, rather than beta-catenin overexpression, induces survivin-mediated resistance to apoptosis in an esophageal cancer cell line

AU - Chang, Elizabeth

AU - Donahue, James

AU - Smith, Anna

AU - Hornick, John

AU - Rao, Jaladanki N.

AU - Wang, Jian Ying

AU - Battafarano, Richard J

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77953479446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953479446&partnerID=8YFLogxK

U2 - 10.1016/j.jtcvs.2009.11.038

DO - 10.1016/j.jtcvs.2009.11.038

M3 - Article

C2 - 20236666

AN - SCOPUS:77953479446

VL - 140

SP - 225

EP - 232

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 1

ER -