title: Protein expression and functional analysis of the FHIT gene in human tumor cells.
abstract: BACKGROUND
  The fragile histidine triad (FHIT) gene at chromosome 3p14.2 has been proposed to be a candidate tumor suppressor gene in human cancers. To test whether FHIT exhibits the functional properties of a tumor suppressor gene, we studied the expression of its protein (pFHIT) in human carcinoma cells and examined the ability of FHIT to inhibit the neoplastic phenotype of cancer cells.
  
  
  METHODS
  Subcellular localization and patterns of protein expression in tumor cells were determined by immunohistochemical analysis and immunoblotting with the use of polyclonal anti-pFHIT antisera. In tumor cells with undetectable pFHIT, we examined the effect of recombinant pFHIT expression on morphology, growth rate, colony formation, and in vivo tumor formation.
  
  
  RESULTS
  We demonstrated that pFHIT is a cytoplasmic 17-kd polypeptide whose expression could not be detected in 30 of 52 human carcinoma cell lines tested. We observed, however, that the stable overexpression of pFHIT did not alter cell morphology, inhibit colony formation, or inhibit cell proliferation in vitro. Furthermore, overexpression of pFHIT did not lead to altered cell cycle kinetics in dividing cells. The in vivo tumorigenicity of a tumor cell line that expressed high levels of recombinant pFHIT was equivalent to that of control transfectants and of parental cells.
  
  
  CONCLUSIONS
  These results suggest that the replacement of pFHIT in human carcinoma cells does not suppress tumor cell growth and that this protein may be involved in tumorigenesis in ways that are distinct from the "classic" tumor suppressor paradigm.
authors.affiliation: Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Otterson
authors.forename: G H
authors.initials: GH
authors.lastname: Xiao
authors.forename: J
authors.initials: J
authors.lastname: Geradts
authors.forename: F
authors.initials: F
authors.lastname: Jin
authors.forename: W D
authors.initials: WD
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Niklinska
authors.forename: F J
authors.initials: FJ
authors.lastname: Kaye
authors.forename: R S
authors.initials: RS
authors.lastname: Yeung
mesh_terms: D018288:Carcinoma, Small Cell / Q000235:genetics; D002873:Chromosome Fragility; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm