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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Lentivirus-mediated RNA interference of Ku70 to enhance radiosensitivity of human mammary epithelial cells
International Journal of Radiation Biology, Volume 86, No. 2, Year 2010
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Description
Purpose: To investigate the radiosensitising effect of Ku autoantigen 70 (Ku70) and Ku autoantigen 80 (Ku80) knockdown by lentivirus-mediated RNA interference (RNAi) in the MCF10A immortalised human mammary epithelial cell line. Materials and methods: MCF10A cells were infected with lentiviral vectors for RNAi of Ku70. The Ku70-knockdown cell line (Ku70i) and a mock-infected control cell line (LVTHM) were used to perform radiation experiments. For the invitro Micronucleus (MN) assay, both cell lines were irradiated with doses of 2 and 4 Gy 60Co γ-rays. For cell survival experiments, doses ranging between 0 and 8 Gy were used. Results: Western blot analysis showed that the Ku70 lentiviral vector was effective in silencing the expression of both Ku70 and Ku80. A significantly higher radiation-induced MN yield was obtained in the Ku70i cell line compared to the control LVTHM cell line. RNAi of Ku70 also resulted in a lower survival yield after irradiation compared to the control cell line. Analysis of cell death mechanisms showed that MCF10A cells (Ku70i and LVTHM) do not undergo apoptosis, but undergo post-irradiation cellular senescence. Conclusion: RNAi of Ku70 resulted in increased chromosomal and cellular radiosensitivity in the MCF10A human mammary cell line after irradiation with 60Co γ-rays. These results further strengthen the role of the Ku protein in correct DNA double strand break (DSB) repair. © 2010 Informa UK Ltd.
Authors & Co-Authors
Vandersickel, Veerle
Belgium, Ghent
Universiteit Gent
Mancini, Monica
Italy, Varese
Università Degli Studi Dell'insubria
Marras, Emanuela
Italy, Varese
Università Degli Studi Dell'insubria
Willems, P.
Belgium, Ghent
Universiteit Gent
Slabbert, Jacobus P.S.
South Africa, Somerset West
Ithemba Laboratory for Accelerator-based Sciences
Philippe, J. J.
Unknown Affiliation
Deschepper, E.
Belgium, Ghent
Universiteit Gent
Thierens, Hubert M.A.
Belgium, Ghent
Universiteit Gent
Perletti, Gianpaolo
Italy, Varese
Università Degli Studi Dell'insubria
Vral, Anne M.
Belgium, Ghent
Universiteit Gent
Statistics
Citations: 10
Authors: 10
Affiliations: 3
Identifiers
Doi:
10.3109/09553000903419940
ISSN:
09553002
e-ISSN:
13623095
Research Areas
Cancer
Genetics And Genomics