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  • Oncogenomics
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cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells

Oncogene volume 22, pages 2680–2688 (2003)Cite this article

Abstract

To investigate changes in gene expression associated with ERBB2, expression profiling of immortalized human mammary luminal epithelial cells and variants expressing a moderate and high level of ERBB2 has been carried out using cDNA microarrays corresponding to approximately 6000 unique genes/ESTs. A total of 61 significantly up- or downregulated (2.0-fold) genes were identified and further validated by RT–PCR analysis as well as microarray comparisons with a spontaneously ERBB2- overexpressing breast cancer cell line and ERBB2-positive primary breast tumors. The expression and clinical relevance of proteins predicted to be associated with ERBB2 overexpression in breast cancers were analysed together with their clinical relevance by antibody screening using a tissue array. Differentially regulated genes include those involved in cell–matrix interactions including proline 4-hydroxylase (P4HA2), galectin 1 (LGALS1) and galectin 3 (LGALS3), fibronectin 1 (FN1) and p-cadherin (CDH3), and cell proliferation (CRIP1, IGFBP3) and transformation (S100P, S100A4). A number of genes associated with MYC signalling were also differentially expressed, including NDRG1, USF2 and the epithelial membrane proteins 1 and 3 (EMP1, EMP3). These data represent profiles of the transcriptional changes associated with ERBB2-related pathways in the breast, and identify novel and potentially useful targets for prognosis and therapy.

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Acknowledgements

The microarray consortium is funded by the Wellcome Trust, the Imperial Cancer Research Fund and the Ludwig Institutes of Cancer Research. We thank the staff of the Sanger Institute Microarray Facility (http://www.sanger.ac.uk/Projects/Microarrays/) for the supply of arrays, lab protocols, and technical advice (David Vetrie, Cordelia Langford, Adam Whittaker, Neil Sutton), Quantarray/GeneSpring datafiles and all data analysis and databases relating to elements on the arrays (Kate Rice, Rob Andrews, Adam Butler, Harish Chudasama). The human I.M.A.G.E. cDNA clone collection was obtained from the MRC HGMP Resource Centre (Hinxton, UK). All cDNA clone resequencing was performed by Team 56 at the Sanger Institute. We are indebted to Professor Ricardo Brentani at the Hospital do Cancer A.C. Camargo, Sao Paulo, Brazil for the tumor RNA. We are grateful to Professors Munro Neville and Alan Ashworth for continued support and helpful discussions pertaining to this project. This work was supported by Breakthrough Breast Cancer.

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  1. Alan Mackay and Chris Jones: These authors contributed equally to this work

Authors and Affiliations

  1. LICR/UCL Breast Cancer Laboratory, University College London, London, UK

    Alan Mackay, Robert A Harris, A Munro Neville & Michael J O'Hare

  2. The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK

    Chris Jones, Tim Dexter, Karen Bulmer, Allison Jones, Peter Simpson & Sunil R Lakhani

  3. Ludwig Institute for Cancer Research, Sao Paolo, Brazil

    Ricardo L A Silva & Luiz F L Reis

  4. Ludwig Institute for Cancer Research, University College London, London, UK

    Parmjit S Jat

  5. Royal Marsden Hospital, London, UK

    Sunil R Lakhani

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  1. Alan Mackay
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  3. Tim Dexter
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  4. Ricardo L A Silva
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Correspondence to Alan Mackay.

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Mackay, A., Jones, C., Dexter, T. et al. cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells. Oncogene 22, 2680–2688 (2003). https://doi.org/10.1038/sj.onc.1206349

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