title: Fhit tumor suppressor: guardian of the preneoplastic genome.
abstract: Environmental agents induce intragenic alterations in the FRA3B/FHIT chromosome fragile site, resulting in fragile FHIT allele loss early in cancer development. Fhit knockout mice are predisposed to tumor development and Fhit gene therapy reduces tumor burden. Repair-deficient cancers are likely to be Fhit-deficient and Fhit-deficient cells show enhanced resistance to ultraviolet C, mitomycin C, camptothecin and oxidative stress-induced cell killing. Loss of Fhit leads to alterations in the DNA damage response checkpoint and contributes to DNA instability. Hsp60/Hsp10 are Fhit interactors, suggesting a direct role for Fhit in stress responses. Fhit also interacts with and stabilizes ferrodoxin reductase (Fdxr), a mitochondrial flavoprotein that transfers electrons from NADPH to cytochrome P450, suggesting a role for Fhit in the modulation of reactive oxygen species production and of genomic damage.
authors.affiliation: Ohio State University Comprehensive Cancer Center, Department of Molecular Virology, Molecular Virology and Medical Genetics. 460 W 12th Avenue, 43210 Columbus, OH, USA.
authors.forename: Flavia
authors.initials: F
authors.lastname: Pichiorri
authors.forename: Tiziana
authors.initials: T
authors.lastname: Palumbo
authors.forename: Sung-Suk
authors.initials: SS
authors.lastname: Suh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Francesco
authors.initials: F
authors.lastname: Trapasso
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Kay
authors.initials: K
authors.lastname: Huebner
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000502:physiology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase