RAD51 can inhibit PDGF-B-induced gliomagenesis and genomic instability Journal Article
| Authors: | Westermark, U. K.; Lindberg, N.; Roswall, P.; Bråsäter, D.; Helgadottir, H. R.; Hede, S. M.; Zetterberg, A.; Jasin, M.; Nistér, M.; Uhrbom, L. |
| Article 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 PDGFB- 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. © The Author(s) 2011. |
| Keywords: | protein expression; gene deletion; nonhuman; flow cytometry; glioma; brain neoplasms; dna replication; cell proliferation; animal cell; animals; mice; mice, knockout; dna damage; homologous recombination; cells, cultured; dna repair; cell differentiation; carcinogenesis; mice, transgenic; immunoenzyme techniques; blotting, western; brain; genomic instability; hyperplasia; tumor cell; fibroblasts; proto-oncogene proteins c-sis; stem cells; green fluorescent proteins; rad51 protein; chickens; rad51 recombinase; platelet derived growth factor b; adp-ribosylation factor 1; pdgf-b; rad51; replicative stress. |
| Journal Title: | Neuro-Oncology |
| Volume: | 13 |
| Issue: | 12 |
| ISSN: | 1522-8517 |
| Publisher: | Oxford University Press |
| Date Published: | 2011-12-01 |
| Start Page: | 1277 |
| End Page: | 1287 |
| Language: | English |
| DOI: | 10.1093/neuonc/nor131 |
| PROVIDER: | scopus |
| PMCID: | PMC3223091 |
| PUBMED: | 21926087 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: NEURJ" - "Source: Scopus" |
