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:

Effects of Herceptin treatment on global gene expression patterns in HER2-amplified and nonamplified breast cancer cell lines

Oncogene volume 23, pages 1010–1013 (2004)Cite this article

Abstract

Herceptin is a humanized monoclonal antibody targeted against the extracellular domain of the HER2 oncogene, which is amplified and overexpressed in 10–34% of breast cancers. Herceptin therapy provides effective treatment in HER2-positive metastatic breast cancer, although a favorable treatment response is not achieved in all cases. Here, we show that Herceptin treatment induces a dose-dependent growth reduction in breast cancer cell lines with HER2 amplification, whereas nonamplified cell lines are practically resistant. Time-course analysis of global gene expression patterns in amplified and nonamplified cell lines indicated a major change in transcript levels between 24 and 48 h of Herceptin treatment. A step-wise gene selection algorithm revealed a set of 439 genes whose temporal expression profiles differed most between the amplified and nonamplified cell lines. The discriminatory power of these genes was confirmed by both hierarchical clustering and self-organizing map analyses. In the amplified cell lines, the Herceptin treatment induced the expression of several genes involved in RNA processing and DNA repair, while cell adhesion mediators and known oncogenes, such as c-FOS and c-KIT, were downregulated. These results provide additional clues to the downstream effects of blocking the HER2 pathway in breast cancer and may provide new targets for more effective treatment.

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

Similar content being viewed by others

References

  • Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC and Norton L . (1996). J. Clin. Oncol., 14, 737–744.

  • Bolstad B, Irizarry R, Astrand M and Speed TA . (2003). Bioinformatics, 19, 185–193.

  • Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME and Shepard HM . (1992). Proc. Natl. Acad. Sci. USA, 89, 4285–4289.

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

  • Cleveland W . (1979). J. Am. Stat. Assoc., 74, 829–836.

  • Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G and Slamon DJ . (1999). J. Clin. Oncol., 17, 2639–2648.

  • Duan R, Xie W, Li X, McDougal A and Safe S . (2002). Biochem. Biophys. Res. Commun., 294, 384–394.

  • Eisen M, Spellman P, Brown P and Botstein D . (1998). Proc. Natl. Acad. Sci. USA, 95, 14863–14868.

  • Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, Sugahara H, Butterfield JH, Ashman LK, Kanayama Y, Matsuzawa Y, Kitamura Y and Kanakura Y . (1993). J. Clin. Invest., 92, 1736–1744.

  • Hautaniemi S, Kauraniemi P, Rämö P, Yli-Harja O, Astola J and Kallioniemi A . (2003a). A Strategy for Identifying Class-Separating Genes in Drug-Treatment Microarray Data. Report 1. Institute of Signal Processing, Tampere University of Technology: Finland, ISBN 952-15-1067-6.

    Google Scholar 

  • Hautaniemi S, Yli-Harja O, Astola J, Kauraniemi P, Kallioniemi A, Wolf M, Ruiz J, Mousses S and Kallioniemi O-P . (2003b). Mach. Learn., 52, 45–66.

  • Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y and Kitamura Y . (1998). Science, 279, 577–580.

  • Hyman E, Kauraniemi P, Hautaniemi S, Wolf M, Mousses S, Rozenblum E, Ringner M, Sauter G, Monni O, Elkahloun A, Kallioniemi OP and Kallioniemi A . (2002). Cancer Res., 62, 6240–6245.

  • Kauraniemi P, Bärlund M, Monni O and Kallioniemi A . (2001). Cancer Res., 61, 8235–8240.

  • Kohonen T (ed). (2001). Self-Organizing Maps, 3rd edn Springer: Heidelberg, Germany.

    Book  Google Scholar 

  • Longley BJ, Reguera MJ and Ma Y . (2001). Leuk. Res., 25, 571–576.

  • Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J and Baselga J . (2001). Cancer Res., 61, 4744–4749.

  • Monni O, Bärlund M, Mousses S, Kononen J, Sauter G, Heiskanen M, Paavola P, Avela K, Chen Y, Bittner ML and Kallioniemi A . (2001). Proc. Natl. Acad. Sci. USA, 98, 5711–5716.

  • Mousses S, Bittner ML, Chen Y, Dougherty ER, Baxevanis A, Meltzer PS and Trent JM . (2000). Functional Genomics: Gene Expression Analysis by cDNA Microarrays, Livesey FJ and Hunt SP (eds). Oxford University Press: Oxford, pp. 113–137.

    Google Scholar 

  • Ross JS and Fletcher JA . (1999). Semin. Cancer Biol., 9, 125–138.

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J and Norton L . (2001). N. Engl. J. Med., 344, 783–792.

  • van der Burg B, van Selm-Miltenburg AJ, de Laat SW and van Zoelen EJ . (1989). Mol. Cell. Endocrinol., 64, 223–228.

  • Vesanto J, Himberg J, Alhoniemi E and Parhankangas J . (2000). SOM Toolbox for Matlab 5. Technical Report A57. Helsinki University of Technology: Finland.

    Google Scholar 

  • Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ and Press M . (2002). J. Clin. Oncol., 20, 719–726.

  • Wilding G, Lippman ME and Gelmann EP . (1988). Cancer Res., 48, 802–805.

  • Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S and Arteaga CL . (2002). Cancer Res., 62, 4132–4141.

  • Yang Y, Dudoit S, Luu P and Speed T . (2001). Microarrays: Optical Technologies and Informatics, Bittner M, Chen Y, Dorsel A and Dougherty E (eds). SPIE, Society for Optical Engineering: San Jose, CA, pp. 141–152.

    Book  Google Scholar 

Download references

Acknowledgements

We thank Ms Kati Rouhento for excellent technical assistance. This work was supported by the Academy of Finland, Foundation for Finnish Cancer Institute, the Medical Research Fund of the Tampere University Hospital, the Science Fund of Tampere, as well as Finnish and Pirkanmaa Cultural Foundations.

Author information

Authors and Affiliations

  1. Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, FIN-33520, Finland

    Päivikki Kauraniemi & Anne Kallioniemi

  2. Institute of Signal Processing, Tampere University of Technology, Tampere, FIN-33101, Finland

    Sampsa Hautaniemi, Reija Autio & Jaakko Astola

  3. Biomedicum Biochip Center, University of Helsinki, Biomedicum Helsinki, Helsinki, FIN-00290, Finland

    Outi Monni

  4. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, 20892, MD, USA

    Abdel Elkahloun

Authors
  1. Päivikki Kauraniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sampsa Hautaniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reija Autio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jaakko Astola
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Outi Monni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abdel Elkahloun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anne Kallioniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Kallioniemi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kauraniemi, P., Hautaniemi, S., Autio, R. et al. Effects of Herceptin treatment on global gene expression patterns in HER2-amplified and nonamplified breast cancer cell lines. Oncogene 23, 1010–1013 (2004). https://doi.org/10.1038/sj.onc.1207200

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207200

Keywords

This article is cited by

Search

Advanced search

Quick links