Abstract
This study shows that in the glioblastoma hamster cell line HJC12 the retinoblastoma family member pRb2/p130 enhances γ-radiation-induced cell death. In HJC12 cells the tetracycline-regulated expression of pRb2/p130 increased the percentage of γ-radiation-induced apoptotic cells from 27 to 47%. pRb2/p130 overexpression was associated with the downregulation of the anti-apoptotic factor Bcl-2 and the upregulation of the steady-state protein levels of the pro-apoptotic transcription factor p73. In particular, RT–PCR showed a significant increase in the expression of the p73δ isoform when pRb2/p130 was overexpressed. The ability of pRb2/p130 to modulate apoptosis was not associated with its role in mediating G0/G1 arrest during cell cycle progression. Our data suggest a role for pRb2/p130 in glioblastoma γ-radiation-induced cell death, indicating that the antitumoral action of pRb2/p130 can regulate both inhibition of cell cycle progression and induction of cell death.
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Acknowledgements
We especially thank Mr Charles Zegar for his support of our research efforts. This work was supported in part by National Institute of Health Grant RO1 CA60999/01A1, by Grant PO1 NS36466 (to A Giordano and K Khalili), by Grant PO1-CA56309 (to A Giordano), by the Sbarro Health Research Organization, by research grant Min. Sanita', Telethon E872, AIRC, MURST-Corn 98, EU grant OLG1-1999-00739 (to G Melino). V Masciullo was supported by a training grant from the National Cancer Institute (PHS 5 T32 CA09137). PP Claudio is the recipient of a fellowship from the ‘Associazione Leonardo di Capua’.
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Pucci, B., Claudio, P., Masciullo, V. et al. pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation. Oncogene 21, 5897–5905 (2002). https://doi.org/10.1038/sj.onc.1205750
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DOI: https://doi.org/10.1038/sj.onc.1205750
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