title: Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death.
abstract: Repression of cell cycle progression by tumor suppressors might provide a means for tumor therapy. Here we demonstrate that ectopic overexpression of the p16INK4/CDKN2 tumor suppressor from an adenovirus vector in various cell lines results in block of cell division and, subsequently, in a gradual reduction of the levels of the product of retinoblastoma susceptibility gene, pRb. Overexpression of p53 and p16INK4/CDKN2, but not p53 on its own, induces apoptotic death only in tumor cells. Simultaneous adenoviral transfer of p16 and p53 genes leads to inhibition of tumor growth in nude mice. These results suggest that combined delivery of two cooperating genes like p16 and p53 could be the basis for the development of a new strategy for cancer gene therapy.
authors.affiliation: Max-Planck-Gesellschaft, Berlin-Buch, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Sandig
authors.forename: K
authors.initials: K
authors.lastname: Brand
authors.forename: S
authors.initials: S
authors.lastname: Herwig
authors.forename: J
authors.initials: J
authors.lastname: Lukas
authors.forename: J
authors.initials: J
authors.lastname: Bartek
authors.forename: M
authors.initials: M
authors.lastname: Strauss
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53