title: Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in breast cancer cell lines.
abstract: The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a tumor suppressor gene that is altered mainly by deletion in a large fraction of human tumors, including breast cancers. To evaluate the potential of FHIT gene therapy in this type of cancer, we have studied the biological effects of adenoviral FHIT transduction (Ad-FHIT) in breast cancer cell lines. The results showed that, after FHIT restoration in BT-549, MDA-MB-436, and HCC1806 cells, they underwent apoptosis by activation of the intrinsic pathway. In all three cell lines infected with Ad-FHIT, we have found activation of caspase-2, which is required for permeabilization of mitochondria, release of cytochrome c, and apoptosis. Furthermore, Fhit overexpression produces alteration in cell cycling properties, as well as reduction of the tumorigenic potential in nude mice.
authors.affiliation: Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sevignani
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Rossano
authors.initials: R
authors.lastname: Cesari
authors.forename: Manuela
authors.initials: M
authors.lastname: Sarti
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Sai
authors.initials: S
authors.lastname: Yendamuri
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchione
authors.forename: Francesco
authors.initials: F
authors.lastname: Trapasso
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D017766:Acid Anhydride Hydrolases; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase