Frequent altered expression of fragile histidine triad protein in human colorectal adenomas.
Fragile histidine triad (FHIT) gene is involved in deletions on the short arm of chromosome 3 in various human cancers. We found that 47% of colorectal adenomas, which is a higher frequency than that of K-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 protein. Additionally, expression of human Fhit protein in human colon carcinoma cell line SW480 exhibited a marked inhibition of growth and rendered SW480 cells highly susceptible to undergo apoptosis compared with control cells. These findings suggest that altered expression of the FHIT gene is a quite early aberration in the development of colorectal tumors and that Fhit protein may act as a tumor suppressor.
Morikawa
H
H
Second Department of Internal Medicine, Osaka Medical College, Daigaku-cho, Takatsuki, Osaka 569-8686, Japan.
Nakagawa
Y
Y
Hashimoto
K
K
Niki
M
M
Egashira
Y
Y
Hirata
I
I
Katsu
K
K
Akao
Y
Y
D017766:Acid Anhydride Hydrolases; D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism*; D053938:DNA Fragmentation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006867:Hydrolases; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D009363:Neoplasm Proteins; D009707:Nucleosomes / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D014176:Protein Biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D006861:Hydrogen Peroxide; D006867:Hydrolases; D009363:Neoplasm Proteins; D009707:Nucleosomes; D016283:Proto-Oncogene Proteins p21(ras); D000099170:Bis(5'-adenosyl)triphosphatase; C097552:histidine triad protein; C501009:HRAS protein, human