Frequent altered expression of fragile histidine triad protein in human colorectal adenomas

Fragile histidine triad (FHIT) gene is involved in deletions on the short a rm of chromosome 3 in various human cancers. We found that 47% of colorecta l adenomas, which is a higher frequency than that of H-ras, showed altered expression of the Fhit protein by Western blot analysis. The amount of Fhit protein was inversely correlated with the degree of dysplasia. Importantly , 27% of low-grade dysplastic adenomas showed altered expression of Fhit pr otein. Additionally, expression of human Fhit protein in human colon carcin oma cell line SW480 exhibited a marked inhibition of growth and rendered SW 480 cells highly susceptible to undergo apoptosis compared with control cel ls. These findings suggest that altered expression of the FHIT gene is a qu ite early aberration in the development of colorectal tumors and that Fhit protein may act as a tumor suppressor. (C) 2000 Academic Press.