Cancer Prevention and Therapy in a Preclinical Mouse Model: Impact of FHIT Viruses

Title: Cancer Prevention and Therapy in a Preclinical Mouse Model: Impact of FHIT Viruses

Volume: 4 Issue: 1

Author(s): Hideshi Ishii, Andrea Vecchione, Louise Y.Y. Fong, Nicola Zanesi, Francesco Trapasso, Yusuke Furukawa, Raffaele Baffa, Kay Huebner and Carlo M. Croce

Affiliation:

Keywords: chromosome, FRA3B, protein, proapoptotic, carcinogen

Abstract: 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.

Cite this article as:

Ishii Hideshi, Vecchione Andrea, Fong Y.Y. Louise, Zanesi Nicola, Trapasso Francesco, Furukawa Yusuke, Baffa Raffaele, Huebner Kay and Croce M. Carlo, Cancer Prevention and Therapy in a Preclinical Mouse Model: Impact of FHIT Viruses, Current Gene Therapy 2004; 4 (1) . https://dx.doi.org/10.2174/1566523044578031