title: Replacement of Fhit in cancer cells suppresses tumorigenicity.
abstract: The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5',5"'-P1,P3-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit function, wild-type and mutant FHIT genes were transfected into cancer cell lines that lacked endogenous Fhit. No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase "dead" Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5',5"'-P1, P3-triphosphate hydrolysis is not required for tumor suppression.
authors.affiliation: Kimmel Cancer Center and Departments of Microbiology-Immunology and Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Siprashvili
authors.forename: G
authors.initials: G
authors.lastname: Sozzi
authors.forename: L D
authors.initials: LD
authors.lastname: Barnes
authors.forename: P
authors.initials: P
authors.lastname: McCue
authors.forename: A K
authors.initials: AK
authors.lastname: Robinson
authors.forename: V
authors.initials: V
authors.lastname: Eryomin
authors.forename: L
authors.initials: L
authors.lastname: Sard
authors.forename: E
authors.initials: E
authors.lastname: Tagliabue
authors.forename: A
authors.initials: A
authors.lastname: Greco
authors.forename: L
authors.initials: L
authors.lastname: Fusetti
authors.forename: G
authors.initials: G
authors.lastname: Schwartz
authors.forename: M A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: K
authors.initials: K
authors.lastname: Huebner
mesh_terms: D017766:Acid Anhydride Hydrolases; D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009363:Neoplasm Proteins; D009368:Neoplasm Transplantation; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; D010727:Phosphoric Diester Hydrolases; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase