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

Biochem Biophys Res Commun. 2000 Nov 11;278(1):205-10. doi: 10.1006/bbrc.2000.3771.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases*
  • Adenoma / metabolism*
  • Adult
  • Aged
  • Apoptosis
  • Blotting, Western
  • Cell Division
  • Chromosomes, Human, Pair 3
  • Cloning, Molecular
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / metabolism*
  • DNA Fragmentation
  • Female
  • Gene Deletion
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hydrolases*
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mucous Membrane / metabolism
  • Neoplasm Proteins*
  • Nucleosomes / metabolism
  • Polymorphism, Single-Stranded Conformational
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins p21(ras) / biosynthesis
  • Rectum / metabolism
  • Rectum / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Neoplasm Proteins
  • Nucleosomes
  • fragile histidine triad protein
  • histidine triad protein
  • Hydrogen Peroxide
  • Hydrolases
  • Acid Anhydride Hydrolases
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)