title: The promoter of the human cystic fibrosis transmembrane conductance regulator gene directing SV40 T antigen expression induces malignant proliferation of ependymal cells in transgenic mice.
abstract: Transgenic mice bearing a human cystic fibrosis transmembrane conductance regulator (CFTR) promoter-SV40 T antigen fusion transgene were generated in order to localize in vivo the potential oncogenesis linked to the tissue-specific activity of the promoter for the CFTR gene. Surprisingly, the only site of tumors resulting from expression of the reporter onc gene was ependymal cells lining the brain ventricles. SV40 T antigen expression in these cells led to a consistent pathology in the first weeks of age: ependymoma and consequent hydrocephaly. Tumor-derived cell lines were established, characterized and shown to originate from SV40 T antigen-induced ependymoma. No pathological alterations were found in other organs, such as lungs and pancreas, in which cystic fibrosis is pathologically manifest in humans. Such transgenic mice and derived cell lines may represent valid models for analysing (1) the role of SV40 T antigen in ependymoma formation and (2) CFTR function in ependymal cells.
authors.affiliation: Department of Animal Systems, Transgene, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Perraud
authors.forename: K
authors.initials: K
authors.lastname: Yoshimura
authors.forename: B
authors.initials: B
authors.lastname: Louis
authors.forename: W
authors.initials: W
authors.lastname: Dalemans
authors.forename: D
authors.initials: D
authors.lastname: Ali-Hadji
authors.forename: H
authors.initials: H
authors.lastname: Schultz
authors.forename: M C
authors.initials: MC
authors.lastname: Claudepierre
authors.forename: C
authors.initials: C
authors.lastname: Chartier
authors.forename: C
authors.initials: C
authors.lastname: Danel
authors.forename: J P
authors.initials: JP
authors.lastname: Bellocq
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000209:etiology; D002277:Carcinoma / Q000209:etiology; D002471:Cell Transformation, Neoplastic; D016545:Choroid Plexus Neoplasms / Q000209:etiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004805:Ependyma / Q000473:pathology*; D004806:Ependymoma / Q000209:etiology; D015967:Gene Expression Regulation, Viral; D005809:Genes, Regulator / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D011401:Promoter Regions, Genetic / Q000502:physiology*; D013539:Simian virus 40
chemical_list: D000957:Antigens, Viral, Tumor; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator