Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Agami R, Blandino G, Oren M, Shaul Y . 1999 Nature 399: 809–813

  • An B, Dou QP . 1996 Cancer Res. 56: 438–442

  • Baldi A, De Luca A, Claudio PP, Baldi F, Giordano GG, Tommasino M, Paggi M, Giordano A . 1995 J. Cell Biochem. 59: 402–408

  • Berry De, Lu Y, Schmidt B, Fallon PG, O'Connell H, Hu SX, Xu HJ, Blanck G . 1996 Oncogene 12: 1809–1819

  • Bowen C, Spiegel S, Gelmann EP . 1998 Cancer Res. 58: 3275–3281

  • Choisy-Rossi C, Yonish-Rouach E . 1999 Cell Death Differ. 5: 1162–1168

  • Claudio PP, Howard CM, Baldi A, De Luca, Fu Y, Condorelli G, Sun Y, Colburn N, Calabretta B, Giordano A . 1994 Cancer Res. 54: 5555–5560

  • Claudio PP, Howard CM, Pacilio C, Cinti C, Romano G, Minimo C, Maraldi NM, Minna JD, Gelbert L, Leoncini L, Tosi GM, Hicheli P, Caputi M, Giordano GG, Giordano A . 2000 Cancer Res. 60: 372–382

  • Cobrinik D, Lee MH, Hannon G, Mulligan G, Bronson RT, Dyson N, Harlow E, Beach D, Weinberg RA, Jacks T . 1996 Genes Dev. 10: 1633–1644

  • Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, Hotz MA, Lassota P, Traganos F . 1992 Cytometry 13: 795–808

  • Debatin KM, Beltinger C, Bohler T, Fellenberg J, Friesen C, Fulda S, Herr I, Loss M, Scheuerpflug C, Sieverts H, Stahnke K . 1997 Bioch. Soc. Trans. 25: 405–410

  • De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M, Levrero M, Melino G . 1998 J. Exp. Med. 188: 1763–1768

  • De Laurenzi V, Catani MV, Costanzo A, Terrinoni A, Corazzari M, Levrero M, Knight RA, Melino G . 1999 Cell Death Differ. 6: 389–390

  • De Laurenzi V, Rossi A, Terrinoni A, Barcaroli D, Levrero M, Costanzo A, Knight RA, Guerrieri P, Melino G . 2000 Biochem. Biophys. Res. Commun. 273: 342–346

  • De Luca A, MacLachlan TK, Bagella L, Dean C, Howard CM, Claudio PP, Baldi A, Khalili K, Giordano A . 1997 J. Biol. Chem. 272: 20971–20974

  • Ding Y, Inoue T, Kamiyama J, Tamura Y, Ohtani-Fujita N, Igata E, Sakai T . 1999 DNA Res. 6: 347–351

  • Dou QP, An B, Antoku K, Johnson DE . 1997 J. Cell. Biochem. 64: 586–594

  • Fan G, Ma X, Kren BT, Steer CJ . 1996 Oncogene 12: 1909–1919

  • Gil-Gomez G, Berns A, Brady HJM . 1998 EMBO J. 17: 7209–7218

  • Gong JG, Costanzo A, Yang HQ, Melino G, Kaelin WG, Levrero M, Wang JYL . 1999 Nature 399: 806–809

  • Gross A, McDonnell JM, Korsmeyer SJ . 1999 Genes Dev. 13: 1899–1911

  • Haas-Kogan DA, Kogan SC, Levi D, Dazin P, T'ang A, Fung YK, Israel MA . 1995 EMBO J. 14: 461–472

  • Harvey KJ, Blomquist JF, Ucker DS . 1998 Mol. Cell. Biol. 18: 2912–2922

  • Howard CM, Claudio PP, Gallia GL, Gordon J, Giordano GG, Hauck WW, Khalili K, Giordano A . 1998 J. Natl. Cancer Inst. 90: 1451–1460

  • Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, Kaelin WG . 2000 Nature 407: 645–648

  • Jacks T, Fazeli A, Schmitt E, Bronson R, Goodell M, Weinberg R . 1992 Nature 359: 295–300

  • Janicke RU, Walker PA, Lin XY, Porter AG . 1996 EMBO J. 15: 6969–6978

  • Jost C, Marin M, Kaelin W . 1997 Nature 38: 191–194

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D . 1997 Cell 90: 809–819

  • Kasten MM, Giordano A . 1998 Cell Death Differ. 5: 132–140

  • Knudsen KE, Weber E, Arden KC, Cavenee WK, Feramisco JR, Knudsen ES . 1999 Oncogene 18: 5239–5245

  • LeCouter JE, Kablar B, Whyte PFM, Ying C, Rudnicki A . 1998 Development 125: 4669–4679

  • Levrero M, De Laurenzi V, Costanzo A, Gong J, Melino G, Wang JYJ . 1999 Cell Death Differ. 6: 1146–1153

  • MacLachlan TK, Sang N, Giordano A . 1995 Crit. Rev. Eukaryot. Gene Expr. 5: 127–156

  • Melino G, Annicchiarico-Petruzzelli M, Piredda L, Candi E, Gentile V, Davies PAJ, Piacentini M . 1994 Mol. Cell. Biol. 14: 6584–6596

  • Mo YY, Beck WT . 1999 Mol. Pharm. 55: 216–222

  • Muschel RJ, Soto DE, McKenna WG, Bernhard EJ . 1998 Oncogene 17: 3359–3363

  • Negrini M, Silini E, Kozak C, Tsujimoto T, Croce C . 1987 Cell 49: 455–463

  • Nevins J . 1998 Cell Growth Differ. 9: 585–593

  • Piacentini M, Annicchiarico-Petruzzelli M, Oliviero S, Piredda L, Biedler JL, Melino G . 1992 Int. J. Cancer 52: 271–278

  • Ray GV, Gordon J, Logan TJ, Hall DJ, De Luca A, Giordano A, Khalili K . 1995 Int. J. Oncol. 7: 801–808

  • Sheard MA, Krammer PH, Zaloudik J . 1999 Br. J. Cancer 80: 1686–1689

  • Stiegler P, Giordano A . 1998 Prog. Mol. Sub. Biol. 20: 25–42

  • Strasser-Wozak EM, Hartmann BL, Geley S, Sgonc R, Bock G, Santos AJ, Hattmannstorfer R, Wolf H, Pavelka M, Kolfer R . 1998 Cell Death Differ. 5: 687–693

  • Vousden HK . 2000 Cell 103: 691–694

  • Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, Lu H, Kharbanda S, Weichselbaum R, Kufe D . 1999 Nature 399: 814–817

  • Zhivotovsky B, Burgess DH, Schlegel J, Porn MI, Vanags D, Orrenius S . 1997 J. Biol. Chem. 64: 43–49

Download references

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’.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Giordano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205750

Keywords

This article is cited by

Search

Quick links