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

研究成果: ジャーナルへの寄稿学術誌査読


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.

ジャーナルJournal of Nucleic Acids Investigation
出版ステータス出版済み - 2010

!!!All Science Journal Classification (ASJC) codes

  • 生化学


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