Fhit modulates the DNA damage checkpoint response

Hideshi Ishii, Koshi Mimori, Hiroshi Inoue, Taeko Inageta, Kazuhiro Ishikawa, Shuho Semba, Teresa Druck, Francesco Trapasso, Kenzaburo Tani, Andrea Vecchione, Carlo M. Croce, Masaki Mori, Kay Huebner

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

In preneoplastic lesions, the DNA damage checkpoint is induced and loss of heterozygosity at the FRA3B/FHIT common chromosome fragile region precedes or is coincident with activation of the checkpoint response in these early stages. Introduction of exogenous Fhit into cells in vitro led to modulation of expression of checkpoint proteins Hus1 and Chk1 at mid-S checkpoint, a modulation that led to induction of apoptosis in esophageal cancer cells but not in noncancerous primary cultures. Mutation of the conserved Fhit tyrosine 114 resulted in failure of this function, confirming the importance of this residue. The results suggest that the DNA damage-susceptible FRA3B/FHIT chromosome fragile region, paradoxically, encodes a protein that is necessary for protecting cells from accumulation of DNA damage through its role in modulation of checkpoint proteins, and inactivation of Fhit contributes to accumulation of abnormal checkpoint phenotypes in cancer development.

Original languageEnglish
Pages (from-to)11287-11292
Number of pages6
JournalCancer Research
Volume66
Issue number23
DOIs
Publication statusPublished - Dec 1 2006

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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