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Future Oncol. 2008 Dec;4(6):815-24. doi: 10.2217/14796694.4.6.815.

Fhit tumor suppressor: guardian of the preneoplastic genome.

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  • 1Ohio State University Comprehensive Cancer Center, Department of Molecular Virology, Molecular Virology and Medical Genetics. 460 W 12th Avenue, 43210 Columbus, OH, USA.

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.

PMID:
19086848
PMCID:
PMC3400506
DOI:
10.2217/14796694.4.6.815
[PubMed - indexed for MEDLINE]
Free PMC Article
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