Effect of adenoviral transduction of the fragile histidine triad gene intoesophageal cancer cells

Reintroduction of a tumor suppressor gene product in cancer cells is a prom ising 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 f requent biallelic alterations of the FHIT gene in numerous tumors, and have demonstrated a tumor suppressor function of Fhit. We have studied the biol ogical effects of adenoviral-FHIT transduction in esophageal cancer cell li nes. Results showed suppression of cell growth in vitro in three of seven e sophageal cancer cell lines, all seven of which showed abundant expression of the transgene. Adenoviral-FHIT expression, but not control adenoviral in fections, induced caspase-dependent apoptosis in two esophageal cancer cell lines, TE14 and TE4, which express no or very little Fhit, respectively. T reatment 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 G( 2)-M and a small apoptotic cell fraction after adenoviral-FHIT transduction . Thus, adenoviral-FHIT expression can inhibit the growth of esophageal can cer cells, at least in part through caspase-dependent apoptosis, suggesting that adenoviral-FHIT infection should be explored as a therapeutic strateg y.