Down-regulation of beta catenin inhibits the growth of esophageal carcinoma cells

Nirmal K. Veeramachaneni, Hirotoshi Kubokura, Li Lin, James A. Pippin, G. Alexander Patterson, Jeffrey A. Drebin, Richard J. Battafarano, W. Roy Smythe, David A. Jones, Raphael Bueno, Dao M. Nguyen

Research output: Contribution to journalArticle

Abstract

Introduction: Esophageal cancer remains a highly lethal malignancy, with therapeutic options of limited efficacy in the majority of patients. Understanding the molecular events involved in the pathogenesis of esophageal cancer offers insight into potential targets for treatment. Beta catenin and Wnt signaling abnormalities are involved in the development of both adenocarcinoma and squamous carcinoma of the esophagus. We hypothesized that down-regulation of beta catenin would inhibit the growth of human esophageal cancer. Methods: A human esophageal squamous cell carcinoma cell line (TE10) was treated with phosphorothioate antisense oligonucleotides to beta catenin. The cells were subsequently assayed for beta catenin mRNA and protein by real-time polymerase chain reaction and Western blot. Beta catenin transcriptional activity was determined by TOPFlash assay. Cell viability and growth was assessed by methyl-thiazol-diphenyl-tetrazolium assay and trypan blue exclusion. A colorimetric assay was employed to assess caspase 3 activity, and flow cytometry was done to determine percentage of cells in a given phase of the cell cycle. Results: Following antisense treatment, beta catenin mRNA and protein concentration were decreased. There was corresponding decrease in beta catenin-transcription factor-dependent transcription. Treatment with beta catenin antisense resulted in significantly decreased cell viability and proliferation. The mechanism appears to be increased induction of apoptosis. Conclusions: These data suggest a potential role for the targeting of beta catenin in the treatment of esophageal cancer.

Original languageEnglish (US)
Pages (from-to)92-98
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume127
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

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

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  • Cite this

    Veeramachaneni, N. K., Kubokura, H., Lin, L., Pippin, J. A., Patterson, G. A., Drebin, J. A., Battafarano, R. J., Smythe, W. R., Jones, D. A., Bueno, R., & Nguyen, D. M. (2004). Down-regulation of beta catenin inhibits the growth of esophageal carcinoma cells. Journal of Thoracic and Cardiovascular Surgery, 127(1), 92-98. https://doi.org/10.1016/j.jtcvs.2003.06.008