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Title: Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature
Authors: Condiotti, R
Goldenberg, D
Giladi, H
Schnitzer-Perlman, T
Waddington, SN
Buckley, SMK
Heim, D
Cheung, W
Themis, M
Coutelle, C
Simerzin, A
Osejindu, E
Wege, H
Themis, M
Galun, E
Keywords: Lentiviral vectors;Gene transfer;Hepatocarcinomas;Liver tumors;E2F
Issue Date: 2014
Publisher: Nature Publishing Group
Citation: Molecular Therapy, 22(1): pp.59-68, (2014)
Abstract: Lentiviral vectors are widely used in basic research and clinical applications for gene transfer and long-term expression; however, safety issues have not yet been completely resolved. In this study, we characterized hepatocarcinomas that developed in mice 1 year after in utero administration of a feline-derived lentiviral vector. Mapped viral integration sites differed among tumors and did not coincide with the regions of chromosomal aberrations. Furthermore, gene expression profiling revealed that no known cancer-associated genes were deregulated in the vicinity of viral integrations. Nevertheless, five of the six tumors exhibited highly significant upregulation of E2F target genes, of which a majority are associated with oncogenesis, DNA damage response, and chromosomal instability. We further show in vivo and in vitro that E2F activation occurs early on following transduction of both fetal mice and cultured human hepatocytes. On the basis of the similarities in E2F target gene expression patterns among tumors and the lack of evidence implicating insertional mutagenesis, we propose that transduction of fetal mice with a feline lentiviral vector induces E2F-mediated major cellular processes that drive hepatocytes toward uncontrolled proliferation culminating in tumorigenesis.
Description: This article is available open access through the publisher’s website at the link below. Copyright @ 2014 The American Society of Gene & Cell Therapy.
ISSN: 1525-0016
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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