FHIT gene therapy prevents tumor development in Fhit-deficient mice

doi:10.1073/pnas.061020098

FHIT gene therapy prevents tumor development in Fhit-deficient mice

Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107

Contributed by Carlo M. Croce

Abstract

The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit ^+/− knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer.

Footnotes

↵ * K.R.D. and H.I. contributed equally to this study.
↵ † To whom reprint requests should be addressed at: Director, Kimmel Cancer Center, 233 South 10th Street, Blumle Life Science Building, Room 1050, Philadelphia, PA 19107-5799. E-mail: C_Croce{at}hendrix.jci.tju.edu.
Abbreviations:

SCJ,

squamocolumnar junction;

NMBA,

N-nitrosomethylbenzylamine;

GFP,

green fluorescent protein;

AAV,

adenoassociated virus;

Ad,

adenovirus;

FHL,

focal hyperplastic lesions;

PCNA,

proliferating cell nuclear antigen