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.