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:

Lack of functional pRb results in attenuated recovery of mRNA synthesis and increased apoptosis following UV radiation in human breast cancer cells

Oncogene volume 21, pages 4481–4489 (2002)Cite this article

Abstract

Lack of functional pRb results in attenuated recovery of mRNA synthesis and increased apoptosis following UV radiation in human breast cancer cells. We have previously demonstrated that a human breast cancer cell line, MDA-MB-468, which lacks the retinoblastoma protein (pRb), is particularly sensitive to low doses of ultraviolet (UV) radiation. These cells are 15–20-fold more sensitive to UV radiation than cells with wild-type pRb. In order to understand the mechanisms of the high apoptotic response of MDA-MB-468 cells to UV radiation, we examined the effects of UV on these cells with regards to both membrane-mediated events and DNA damage. We found that MDA-MB-468 cells were resistant to all ligand-induced death receptor signaling. In addition, although UV activated caspase 8 in MDA-MB-468 cells, a peptide inhibitor of caspase 8 failed to inhibit UV-induced apoptosis. We then tested the possibility that nuclear events mediated the enhanced sensitivity to UV-induced apoptosis in these cells. Unlike UV-resistant cells, MDA-MB-468 cells were unable to recover mRNA synthesis after 5 J/m2 UVC. We also found that the pRb-null DU-145 cells similarly had attenuated recovery of mRNA synthesis after UV radiation. In UV-resistant cells with wild-type pRb, the inactivation of pRb with HPV-16 E7 resulted in significant inhibition in their ability to recover mRNA synthesis and increased levels of apoptosis following UV radiation. Furthermore, pRb-null cells were deficient in repair of UV radiation-induced DNA damage. These data suggest that the sensitivity of MDA-MB-468 cells to UV radiation is due to defects in repair of DNA damage and recovery of mRNA synthesis rather than to membrane death receptor pathways. Inactivation of pRb may contribute to an increased sensitivity to UV radiation by attenuating repair of DNA lesions and recovery of mRNA synthesis following UV radiation.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Addison CL, Hitt M, Kunsken D, Graham FL . 1997 J. Gen. Virol. 78: 1653–1661

  • Assefa Z, Vantieghem A, Garmyn M, Declercq W, Vandenabeele P, Vandenheede JR, Bouillon R, Merlevede W, Agostinis P . 2000 J. Biol. Chem. 275: 21416–21421

  • Band V, De Caprio JA, Delmolino L, Kulesa V, Sager R . 1991 J. Virol. 65: 6671–6676

  • Band V, Zajchowski D, Kulesa V, Sager R . 1990 Proc. Natl. Acad. Sci. USA 87: 463–467

  • Belka C, Heinrich V, Marini P, Faltin H, Schulze-Osthoff K, Bamberg M, Budach W . 1999a Int. J. Radiat. Biol. 75: 1257–1264

  • Belka C, Marini P, Lepple-Wienhues A, Budach W, Jekle A, Los M, Lang F, Schulze-Osthoff K, Gulbins E, Bamberg M . 1999b Oncogene 18: 4983–4992

  • Belka C, Rudner J, Wesselborg S, Stepczynska A, Marini P, Lepple-Wienhues A, Faltin H, Bamberg M, Budach W, Schulze-Osthoff K . 2000 Oncogene 19: 1181–1190

  • Bookstein R, Shew J, Chen P, Scully P, Lee W . 1990 Science 24: 712–715

  • Boyer SN, Wazer DE, Band V . 1996 Cancer Res. 56: 4620–4624

  • Budihardjo I, Oliver H, Lutter M, Luo X, Wang X . 1999 Annu. Rev. Cell Dev. Biol. 15: 269–290

  • Carlson CA, Ethier SP . 2000 Rad. Res. 154: 590–599

  • Carroll AG, Voeller HJ, Sugars L, Gelmann EP . 1993 Prostate 23: 123–134

  • Conforti G, Nardo T, D'Incalci M, Stefanini M . 2000 Oncogene 19: 2714–2720

  • de Laat WL, Jaspers NG, Hoeijmakers JH . 1999 Genes Dev. 13: 768–785

  • Fan G, Ma X, Kren BT, Rice M, Kmiec EB, Steer CJ . 1997 J. Biol. Chem. 272: 19413–19417

  • Ferrari D, Stepczynska A, Los M, Wesselborg S, Schulze-Osthoff K . 1998 J. Exp. Med. 188: 979–984

  • Game JC, Kaufman PD . 1999 Genetics 151: 485–497

  • Havre PA, Rice MC, Noe M, Kmiec EB . 1998 Cancer Res. 58: 4733–4739

  • Jones DL, Munger K . 1996 Semin. Cancer Biol. 7: 327–337

  • Kennedy BK, Barbie DA, Classon M, Dyson N, Harlow E . 2000 Genes Dev. 14: 2855–2868

  • Kulms D, Poppelmann B, Yarosh D, Luger T, Krutmann J, Schwarz T . 1999 Proc. Natl. Acad. Sci. USA 96: 7974–7979

  • Ljungman M, Zhang F . 1996 Oncogene 13: 823–831

  • Ljungman M, Zhang F, Chen F, Rainbow AJ, McKay BC . 1999 Oncogene 18: 583–592

  • Martini E, Roche DM, Marheineke K, Verreault A, Almouzni G . 1998 J. Cell Biol. 143: 563–575

  • McDougall JK . 1994 Curr. Top. Microbiol. Immunol. 186: 101–119

  • McKay B, Ljungman M, Rainbow A . 1998 Oncogene 17: 545–555

  • McKay BC, Chen F, Clarke ST, Wiggin HE, Harley LM, Ljungman M . 2001 Mutat. Res. 485: 93–105

  • McKay BC, Chen F, Perumalswami CR, Zhang F, Ljungman M . 2000 Mol. Biol. Cell 11: 2543–2551

  • McKay BC, Ljungman M . 1999 Neoplasia 1: 276–284

  • McKay BC, Ljungman M, Rainbow AJ . 1999 Carcinogenesis 20: 1389–1396

  • Rehemtulla A, Hamilton C, Chinnaiyan A, Dixit V . 1997 J. Biol. Chem. 272: 25783–25786

  • Rubin SJ, Hallahan DE, Ashman CR, Brachman DG, Beckett MA, Virudachalam S, Yandell DW, Weichselbaum RR . 1991 J. Surg. Oncol. 46: 31–36

  • Sachsenmaier C, Radler-Pohl A, Zinck R, Nordheim A, Herrlich P, Rahmsdorf HJ . 1994 Cell 78: 963–972

  • Sartor CI, Dziubinski ML, Yu CL, Jove R, Ethier SP . 1997 Cancer Res. 57: 978–987

  • Scheffner M, Romanczuk H, Munger K, Huibregtse JM, Mietz JA, Howley PM . 1994 Curr. Top. Microbiol. Immunol. 186: 83–99

  • Seavey SE, Holubar M, Saucedo LJ, Perry ME . 1999 J. Virol. 73: 7590–7598

  • Sheikh MS, Antinore M, Huang Y . 1998 Oncogene 17: 2555–2563

  • Slee EA, Adrain C, Martin SJ . 1999 Cell Death Differ. 6: 1067–1074

  • Taneja N, Tjalkens R, Philbert MA, Rehemtulla A . 2001 Oncogene 20: 167–177

  • Therrien JP, Drouin R, Baril C, Drobetsky EA . 1999 Proc. Natl. Acad. Sci. USA 96: 15038–15043

  • Webber MM, Bello D, Quader S . 1997 Prostate 30: 136–142

  • Wesselborg S, Engels IH, Rossmann E, Los M, Schulze-Osthoff K . 1999 Blood 93: 3053–3063

  • Zhu Q, Wani MA, El-Mahdy M, Wani AA . 2000 J. Biol. Chem. 275: 11492–11497

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Comprehensive Cancer Center, Ann Arbor, 48109, Michigan, MI, USA

    Christine A Billecke, Mats E Ljungman, Alnawaz Rehemtulla, Neelam Taneja & Stephen P Ethier

  2. Department of Radiology, Centre for Cancer Therapeutics, Ottawa Regional Cancer Center, University of Ottawa, Ottawa, K1H 1C4, Ontario, Canada

    Bruce C McKay

Authors
  1. Christine A Billecke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mats E Ljungman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce C McKay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alnawaz Rehemtulla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neelam Taneja
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stephen P Ethier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen P Ethier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Billecke, C., Ljungman, M., McKay, B. et al. Lack of functional pRb results in attenuated recovery of mRNA synthesis and increased apoptosis following UV radiation in human breast cancer cells. Oncogene 21, 4481–4489 (2002). https://doi.org/10.1038/sj.onc.1205546

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205546

Keywords

This article is cited by

Search

Advanced search

Quick links