Effects of herceptin treatment on global gene expression patterns in her2-amplified and nonamplified breast cancer cell lines

Effects of herceptin treatment on global gene expression patterns in her2-amplified and nonamplified breast cancer cell lines

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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. Access through your institution Buy or subscribe This is a preview of


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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 * Laboratory of Cancer Genetics, Institute of Medical Technology,


University of Tampere and Tampere University Hospital, Tampere, FIN-33520, Finland Päivikki Kauraniemi & Anne Kallioniemi * Institute of Signal Processing, Tampere University of


Technology, Tampere, FIN-33101, Finland Sampsa Hautaniemi, Reija Autio & Jaakko Astola * Biomedicum Biochip Center, University of Helsinki, Biomedicum Helsinki, Helsinki, FIN-00290,


Finland Outi Monni * Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, 20892, MD, USA Abdel Elkahloun Authors * Päivikki Kauraniemi View author publications


You can also search for this author inPubMed Google Scholar * Sampsa Hautaniemi View author publications You can also search for this author inPubMed Google Scholar * Reija Autio View author


publications You can also search for this author inPubMed Google Scholar * Jaakko Astola View author publications You can also search for this author inPubMed Google Scholar * Outi Monni


View author publications You can also search for this author inPubMed Google Scholar * Abdel Elkahloun View author publications You can also search for this author inPubMed Google Scholar *


Anne Kallioniemi View author publications You can also search for this author inPubMed 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: 26 May 2003 * Revised: 02 September 2003 *


Accepted: 10 September 2003 * Published: 01 December 2003 * Issue Date: 29 January 2004 * DOI: https://doi.org/10.1038/sj.onc.1207200 SHARE THIS ARTICLE Anyone you share the following link


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content-sharing initiative KEYWORDS * _HER2_ * herceptin * amplification * breast cancer * cDNA microarray