FHIT suppresses inflammatory carcinogenic activity by inducing apoptosis in esophageal epithelial cells

Koshi Mimori, Takehiko Yokobori, Masaaki Iwatsuki, Tomoya Sudo, Fumiaki Tanaka, Kohei Shibata, Hideshi Ishii, Masaki Mori

Research output: Contribution to journalArticle

Abstract

We focused on the mechanism by which FHIT suppresses neoplastic transformation in normal but damaged esophageal epithelial cells exposed to inflammatory stimuli in vivo and to chemo-radiotherapy in clinical samples. For in vitro analysis, Adenoviral-FHIT (Ad-FHIT) in TE4 and TE2 were used for microarray analysis. For in vivo analysis, wild-type (WT) FHIT and FHIT-deficient (KO) C57BL/6 mice were exposed to N-nitrosomethylbenzylamine (NMBA) and to a cyclooxygenase-2 inhibitor (COXI). Considering DNA damage on clinical samples, expressions of FHIT, BAX and PCNA were evaluated by comparing between 3 cases of esophageal cancer cases of the chemo-radiotherapy responder and 7 cases of the non-responder. In in vitro analysis, we listed the down-regulated genes in Ad-FHIT that significantly control Lac-Z infected cells, such as prostaglandin E receptor 4, cyclooxygenase-1 and cyclooxygenase-2. In in vivo analysis, FHIT-KO mice were much more susceptible to tumorigenesis than were FHIT-WT mice. A significant difference in PGE2 activation was observed between FHIT-WT mice (5.2 ng/mL) and FHIT-KO mice (28.4 ng/mL) after exposure to NMBA in the absence of COXI as determined by ELISA assay (P<0.01). BAX expression was significantly higher in FHIT-WT (1.0±0.43) than in FHIT-KO (0.17±0.17) (P<0.05). The IHC score for FHIT and BAX expression was significantly higher in responders than the others (P<0.05). FHIT possesses tumor suppressor activity by induction of apoptosis in damaged cells after exposure to inflammatory carcinogens and DNA damaging chemo-radiotherapy.

Original languageEnglish
Pages (from-to)31-35
Number of pages5
JournalJournal of Nucleic Acids Investigation
Volume1
Issue number1
DOIs
Publication statusPublished - Dec 1 2010

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All Science Journal Classification (ASJC) codes

  • Biochemistry

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