Cancer prevention and therapy in a preclinical mouse model: impact of FHIT viruses.
A link between common chromosome fragile sites and frequent chromosomal deletions in cancer was observed two decades ago and led to the hypothesis that genes at fragile sites may play a role in tumor development. In 1996, the human fragile histidine triad gene, FHIT, was identified by positional cloning of the chromosome region spanning the carcinogen-sensitive, common fragile site, FRA3B at 3p14.2. Loss or inactivation of the FHIT gene in a large fraction of human tumors results in absence or reduction of Fhit protein. In vitro analyses and in vivo tumorigenicity studies show that restoration of Fhit protein induces tumor suppression in 50% of tumor cell lines tested. Viral vector-mediated FHIT gene transfer to Fhit-deficient mice not only prevents but reverses the carcinogen-induced tumor development in vivo, in accordance with the oncosuppressive properties of Fhit protein. The strong proapoptotic activity following Fhit infection of cancer cells strengthens the case for further exploration of FHIT gene therapy in cancer prevention and treatment.
Ishii
Hideshi
H
Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan. hishii@ms.jichi.ac.jp
Vecchione
Andrea
A
Fong
Louise Y Y
LY
Zanesi
Nicola
N
Trapasso
Francesco
F
Furukawa
Yusuke
Y
Baffa
Raffaele
R
Huebner
Kay
K
Croce
Carlo M
CM
D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002274:Carcinogens, Environmental / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D043283:Chromosome Fragile Sites / Q000235:genetics; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000517:prevention & control / Q000628:therapy*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D002274:Carcinogens, Environmental; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase