Effect of adenoviral transduction of the fragile histidine triad gene into esophageal cancer cells

Hideshi Ishii, Kristoffel R. Dumon, Andrea Vecchione, Francesco Trapasso, Koshi Mimori, Hansjuerg Alder, Masaki Mori, Gabriella Sozzi, Raffaele Baffa, Kay Huebner, Carlo M. Croce

Research output: Contribution to journalArticle

Abstract

Reintroduction of a tumor suppressor gene product in cancer cells is a promising strategy for cancer gene therapy. The fragile histidine triad (FHIT) gene has been identified in a region at chromosome 3p14.2, which is deleted in many tumors, including esophageal cancer. Previous studies have shown frequent biallelic alterations of the FHIT gene in numerous tumors, and have demonstrated a tumor suppressor function of Fhit. We have studied the biological effects of adenoviral-FHIT transduction in esophageal cancer cell lines. Results showed suppression of cell growth in vitro in three of seven esophageal cancer cell lines, all seven of which showed abundant expression of the transgene. Adenoviral-FHIT expression, but not control adenoviral infections, induced caspase-dependent apoptosis in two esophageal cancer cell lines, TE14 and TE4, which express no or very little Fhit, respectively. Treatment of TE14 cells with adenoviral-FHIT vectors resulted in abrogation of tumorigenicity in nude mice. A third esophageal cancer cell line, TE12, without detectable endogenous Fhit, showed accumulation of cells at S to G2-M and a small apoptotic cell fraction after adenoviral-FHIT transduction. Thus, adenoviral-FHIT expression can inhibit the growth of esophageal cancer cells, at least in part through caspase-dependent apoptosis, suggesting that adenoviral-FHIT infection should be explored as a therapeutic strategy.

Original languageEnglish
Pages (from-to)1578-1584
Number of pages7
JournalCancer Research
Volume61
Issue number4
Publication statusPublished - Feb 15 2001

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Ishii, H., Dumon, K. R., Vecchione, A., Trapasso, F., Mimori, K., Alder, H., Mori, M., Sozzi, G., Baffa, R., Huebner, K., & Croce, C. M. (2001). Effect of adenoviral transduction of the fragile histidine triad gene into esophageal cancer cells. Cancer Research, 61(4), 1578-1584.