title: RNAi-mediated knockdown ofE2F2inhibits tumorigenicity of human glioblastoma cells.
abstract: In a previous genome-wide expression profiling study, we identifiedE2F2as a hyperexpressed gene in stem-like cells of distinct glioblastoma multiforme (GBM) specimens. Since the encoded E2F2 transcription factor has been implicated in both tumor suppression and tumor development, we conducted a functional study to investigate the pertinence ofE2F2to human gliomagenesis.E2F2expression was knocked down by transfecting U87MG cells with plasmids carrying a specific silencing shRNA. UponE2F2silencing,in vitrocell proliferation was significantly reduced, as indicated by a time-course analysis of viable tumor cells. Anchorage-independent cell growth was also significantly inhibited afterE2F2silencing, based on cell colony formation in soft agar. Subcutaneous and orthotopic xenograft models of GBM in nude mice also indicated inhibition of tumor developmentin vivo,followingE2F2silencing. As expression of theE2F2gene is associated with glioblastoma stem cells and is involved in the transformation of human astrocytes, the present findings suggest that E2F2 is involved in gliomagenesis and could be explored as a potential therapeutic target in malignant gliomas.
authors.affiliation: Department of Neurology and Neurosurgery, Experimental Neurology Unit, Federal University of São Paulo, São Paulo 04023-900, Brazil ; Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Nakahata
authors.affiliation: Department of Neurology and Neurosurgery, Experimental Neurology Unit, Federal University of São Paulo, São Paulo 04023-900, Brazil ; Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Suzuki
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Rodini
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Mayara L
authors.initials: ML
authors.lastname: Fiuza
authors.affiliation: Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Oswaldo K
authors.initials: OK
authors.lastname: Okamoto
keywords: E2F2; cancer; glioblastoma multiforme; tumorigenesis