title: RAD51 can inhibit PDGF-B-induced gliomagenesis and genomic instability.
abstract: Faithful replication and DNA repair are vital for maintenance of genome integrity. RAD51 is a central protein in homologous recombination repair and during replication, when it protects and restarts stalled replication forks. Aberrant RAD51 expression occurs in glioma, and high expression has been shown to correlate with prolonged survival. Furthermore, genes involved in DNA damage response (DDR) are mutated or deleted in human glioblastomas, corroborating the importance of proper DNA repair to suppress gliomagenesis. We have analyzed DDR and genomic instability in PDGF-B-induced gliomas and investigated the role of RAD51 in glioma development. We show that PDGF-B-induced gliomas display genomic instability and that co-expression of RAD51 can suppress PDGF-B-induced tumorigenesis and prolong survival. Expression of RAD51 inhibited proliferation and genomic instability of tumor cells independent of Arf status. Our results demonstrate that the RAD51 pathway can prevent glioma initiation and maintain genome integrity of induced tumors, suggesting reactivation of the RAD51 pathway as a potential therapeutic avenue.
authors.affiliation: Karolinska Institutet, Department of Oncology-Pathology, Stockholm, Sweden. ulrica.westermark@ki.se
authors.forename: Ulrica K
authors.initials: UK
authors.lastname: Westermark
authors.forename: Nanna
authors.initials: N
authors.lastname: Lindberg
authors.forename: Pernilla
authors.initials: P
authors.lastname: Roswall
authors.forename: Daniel
authors.initials: D
authors.lastname: Bråsäter
authors.forename: Hildur R
authors.initials: HR
authors.lastname: Helgadottir
authors.forename: Sanna-Maria
authors.initials: SM
authors.lastname: Hede
authors.forename: Anders
authors.initials: A
authors.lastname: Zetterberg
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: Monica
authors.initials: M
authors.lastname: Nistér
authors.forename: Lene
authors.initials: L
authors.lastname: Uhrbom
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D042822:Genomic Instability; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D049452:Green Fluorescent Proteins / Q000235:genetics; D059765:Homologous Recombination; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D020574:Proto-Oncogene Proteins c-sis; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D020823:ADP-Ribosylation Factor 1