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.

  • Short Report
  • Published:

Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses

Oncogene volume 18, pages 3666–3672 (1999)Cite this article

Abstract

The fate of cells exposed to ionizing radiation (IR) may depend greatly on changes in gene expression, so that an improved view of gene induction profiles is important for understanding mechanisms of checkpoint control, repair and cell death following such exposures. We have used a quantitative fluorescent cDNA microarray hybridization approach to identify genes regulated in response to γ-irradiation in the p53 wild-type ML-1 human myeloid cell line. Hybridization of the array to fluorescently-labeled RNA from treated and untreated cells was followed by computer analysis to derive relative changes in expression levels of the genes present in the array, which agreed well with actual quantitative changes in expression. Forty-eight sequences, 30 not previously identified as IR-responsive, were significantly regulated by IR. Induction by IR and other stresses of a subset of these genes, including the previously characterized CIP1/WAF1, MDM2 and BAX genes, as well as nine genes not previously reported to be IR-responsive, was examined in a panel of 12 human cell lines. Responses varied widely in cell lines with different tissues of origin and different genetic backgrounds, highlighting the importance of cellular context to genotoxic stress responses. Two of the newly identified IR-responsive genes, FRA-1 and ATF3, showed a p53-associated component to their IR-induction, and this was confirmed both in isogenic human cell lines and in mouse thymus. The majority of the IR-responsive genes, however, showed no indication of p53-dependent regulation, representing a potentially important class of stress-responsive genes in leukemic cells.

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

Similar content being viewed by others

References

  • Ariizumi K, Bergstresser PR and Takashima A. . 1996 J. Dermatol. Sci. 12: 147–155.

  • Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G and Thompson CB. . 1993 Cell 74: 597–608.

  • Chen BP, Liang G, Whelan J and Hai T. . 1994a J. Biol. Chem. 269: 15819–15826.

  • Chen BP, Wolfgang CD and Hai T. . 1996 Mol. Cell. Biol. 16: 1157–1168.

  • Chen CY, Oliner JD, Zhan Q, Fornace Jr AJ, Vogelstein B and Kastan MB. . 1994b Proc. Natl. Acad. Sci. USA 91: 2684–2688.

  • Chen Y, Dougherty ER and Bittner ML. . 1997 J. Biomed. Optics 2: 364–374.

  • Chittenden T, Harrington EA, O'Connor R, Flemington C, Lutz RJ, Evan GI and Guild BC. . 1995 Nature 374: 733–736.

  • Cohen DR and Curran T. . 1988 Mol. Cell. Biol. 8: 2063–2069.

  • Cuomo CA, Kirch SA, Gyuris J, Brent R and Oettinger MA. . 1994 Proc. Natl. Acad. Sci. USA 91: 6156–6160.

  • DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA and Trent JM. . 1996 Nat. Genet. 14: 457–460.

  • Donehower LA, Harvey M, Slagle BL, McArther MJ, Montgomery Jr CA, Butel JS and Bradley A. . 1992 Nature 356: 215–221.

  • El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B. . 1993 Cell 75: 817–825.

  • Fan CM and Maniatis T. . 1990 Genes Dev. 4: 29–42.

  • Fargnoli J, Holbrook NJ and Fornace Jr AJ. . 1990 Anal. Biochem. 187: 364–373.

  • Fornace Jr AJ. . 1992 Ann. Rev. Genetics 26: 507–526.

  • Gorospe M, Martindale JL, Sheikh MS, Fornace Jr AL and Holbrook NJ. . 1996 Mol. Cell. Differentiation 4: 47–65.

  • Hagmeyer BM, Duyndam MC, Angel P, de Groot RP, Verlaan M, Elfferich P, van der Eb A and Zantema A. . 1996 Oncogene 12: 1025–1032.

  • Heller RA, Schena M, Chai A, Shalon D, Bedilion T, Gilmore J, Woolley DE and Davis RW. . 1997 Proc. Natl. Acad. Sci. USA 94: 2150–2155.

  • Holbrook NJ, Liu Y and Fornace Jr AJ. . 1996 In: Stress-inducible Cellular Responses. Feige U, Morimoto RI, Yahara I and Polla BS. (eds).. Birkhauser Verlag: Basel, Switzerland. pp. 273–288.

    Book  Google Scholar 

  • Hollander MC and Fornace Jr AJ. . 1990 Biotechniques 9: 174–179.

  • Hsu JC, Bravo R and Taub R. . 1992 Mol. Cell. Biol. 12: 4654–4665.

  • Ivanov VN, Deng G, Podack ER and Malek TR. . 1995 Int. Immunol. 7: 1709–1720.

  • Ko LJ and Prives C. . 1996 Genes Dev. 10: 1054–1072.

  • Komarova EA, Diatchenko L, Rokhlin OW, Hill JE, Wang ZJ, Krivokrysenko VI, Feinstein E and Gudkov AV. . 1998 Oncogene 17: 1089–1096.

  • Lashkari DA, DeRisi JL, McCusker JH, Namath AF, Gentile C, Hwang SY, Brown PO and Davis RW. . 1997 Proc. Natl. Acad. Sci. USA 94: 13057–13062.

  • Liang G, Wolfgang CD, Chen BP, Chen TH and Hai T. . 1996 J. Biol. Chem. 271: 1695–1701.

  • Liou HC, Sha WC, Scott ML and Baltimore D. . 1994 Mol. Cell. Biol. 14: 5349–5359.

  • Madden SL, Galella EA, Zhu J, Bertelsen AH and Beaudry GA. . 1997 Oncogene 15: 1079–1085.

  • Perry ME, Piette J, Zawadzki JA, Harvey D and Levine AJ. . 1993 Proc. Natl. Acad. Sci. USA 90: 11623–11627.

  • Polyak K, Xia Y, Zweler JL, Kinzler KW and Vogelstein B. . 1997 Nature 389: 300–306.

  • Rothe M, Pan MG, Henzel WJ, Ayres TM and Goeddel DV. . 1995 Cell 83: 1243–1252.

  • Schena M, Shalon D, Davis RW and Brown PO. . 1995 Science 270: 467–470.

  • Schena M, Shalon D, Heller R, Chai A, Brown PO and Davis RW. . 1996 Proc. Natl. Acad. Sci. USA 93: 10614–10619.

  • Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M and Chretien M. . 1991 Genomics 11: 103–107.

  • Smith ML, Chen IT, Zhan Q, O'Connor PM and Fornace Jr AJ. . 1995 Oncogene 10: 1053–1059.

  • Smith ML and Fornace Jr AJ. . 1996a Mutation Res. 340: 109–124.

  • Smith ML and Fornace Jr AJ. . 1996b Am. J. Pathol. 148: 1019–1022.

  • Velculescu VE, Zhang L, Vogelstein B and Kinzler KW. . 1995 Science 270: 484–487.

  • Zhan Q, Carrier F and Fornace Jr AJ. . 1993 Mol. Cell. Biol. 13: 4242–4250.

  • Zhan Q, Bae I, Kastan MB and Fornace Jr AJ. . 1994a Cancer Res. 54: 2755–2760.

  • Zhan Q, Fan S, Bae I, Guillouf C, Liebermann DA, O'Connor PM and Fornace Jr AJ. . 1994b Oncogene 9: 3743–3751.

  • Zhan Q, El-Deiry W, Bae I, Alamo Jr I, Kastan MB, Vogelstein B and Fornace Jr AJ. . 1995 Int. J. Oncology 6: 937–946.

  • Zhan Q, Alamo Jr I, Yu K, Boise LH, O'Connor PM and Fornace Jr AJ. . 1996 Oncogene 13: 2287–2293.

  • Zhan Q, Bae I, Fornace Jr AJ and Craig RW. . 1997 Oncogene 14: 1031–1039.

  • Zhang Q, Didonato JA, Karin M and McKeithan TW. . 1994 Mol. Cell. Biol. 14: 3915–3926.

Download references

Acknowledgements

We would like to thank Stephen B Leighton, Thomas Pohida and Paul D Smith for their contributions to instrumentation design, Yuan Jiang and Gerald C Gooden for their contributions to the microarray studies, and Khanh T Do for technical assistance. This work was supported in part by DOE grant ER62683.

Author information

Authors and Affiliations

  1. National Institutes of Health, National Cancer Institute, Bethesda, MD 20892, Maryland, USA

    Sally A Amundson & Albert J Fornace Jr

  2. National Human Genome Research Institute, Bethesda, MD 20892, Maryland, USA

    Mike Bittner, Yidong Chen, Jeffrey Trent & Paul Meltzer

Authors
  1. Sally A Amundson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mike Bittner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yidong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey Trent
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Albert J Fornace Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amundson, S., Bittner, M., Chen, Y. et al. Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses. Oncogene 18, 3666–3672 (1999). https://doi.org/10.1038/sj.onc.1202676

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202676

Keywords

This article is cited by

Search

Advanced search

Quick links