REPLACEMENT OF FHIT IN CANCER-CELLS SUPPRESSES TUMORIGENICITY

The candidate tumor suppressor gene, FHIT, encompasses the common huma n chromosomal fragile site at 3p14.2, the hereditary renal cancer tran slocation breakpoint, and cancer cell homozygous deletions. Fhit hydro lyzes dinucleotide 5',5'''-P-1,P-3-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit fun ction, wild-type and mutant FHIT genes were transfected into cancer ce ll lines that lacked endogenous Fhit. No consistent effect of exogenou s Fhit on growth in culture was observed, but Fhit and hydrolase ''dea d'' Fhit mutant proteins suppressed tumorigenicity in nude mice, indic ating that 5',5'''-P-1,P-3-triphosphate hydrolysis is not required for tumor suppression.