title: Enhanced tumour cell nuclear targeting in a tumour progression model.
abstract: BACKGROUND
  There is an urgent need for new approaches to deliver bioactive molecules to cancer cells efficiently and specifically.
  
  
  METHODS
  Here we fuse the cancer cell nuclear targeting module of the Chicken Anaemia Virus Apoptin protein to the core histones H2B and H3 and utilise them in transfection, protein transduction and DNA binding assays.
  
  
  RESULTS
  We found subsequent nuclear accumulation of these proteins to be 2-3 fold higher in tumour compared to normal cells in transfected isogenic human osteosarcoma and breast tumour progression models. This represents the first demonstration of enhanced nuclear targeting by Apoptin in a tumour progression model, and its functionality in a heterologous protein context. Excitingly, we found that the innate transduction ability of histones could be exploited in combination with the Apoptin nuclear targeting module to effect an overall 13-fold higher delivery of protein to osteosarcoma cancer cell nuclei compared to their isogenic normal counterparts.
  
  
  CONCLUSIONS
  This is the first report of cancer-cell specificity by a cell penetrating protein, with important implications for the use of protein transduction as a vehicle for gene/drug delivery in the future, and in particular in the development of highly specific and effective anti-cancer agents.
authors.affiliation: Nuclear Signalling Laboratory, Department Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia. michael.nastasie@monash.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Nastasie
authors.affiliation: CSIRO Molecular and Health Technologies, Bayview Avenue, Clayton, Victoria, 3168, Australia. michael.nastasie@monash.edu.
authors.forename: Helmut
authors.initials: H
authors.lastname: Thissen
authors.affiliation: Nuclear Signalling Laboratory, Department Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia. David.Jans@monash.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
authors.affiliation: Nuclear Signalling Laboratory, Department Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia. kylie.wagstaff@monash.edu.
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Wagstaff
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009928:Organ Specificity; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D036022:Capsid Proteins; D006657:Histones; D011993:Recombinant Fusion Proteins; C091717:VP3 protein, Chicken anemia virus