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Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation

Oncogene volume 19, pages 5471–5476 (2000)Cite this article

Abstract

A high proportion of human breast cancers, in contrast with normal mammary tissue, express the intracellular tyrosine kinase BRK. BRK expression enhances the mitogenic response of mammary epithelial cells to epidermal growth factor, and conferment of a proliferative advantage through this mechanism may account for the frequent elevation of BRK expression in tumours. Here we report that BRK expression in mammary epithelial cells, at pathologically relevant levels, results in an enhanced phosphorylation of the epidermal growth factor receptor-related receptor erbB3 in response to epidermal growth factor. As a consequence, erbB3 recruits increased levels of phosphoinositide 3-kinase, and this is associated with a potentiated activation of Akt. This effect of BRK on the regulation of phosphoinositide 3-kinase and Akt activity may account for BRK's ability to enhance mammary cell mitogenesis, and raises the possibility that breast tumours expressing BRK may acquire a resistance to pro-apoptotic signals.

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Acknowledgements

The authors thank Dr Ian Hiles (GlaxoWellcome, Stevenage, UK) for the gift of the human erbB3 cDNA.MR Crompton is supported by a research grant from the School of Biological Sciences, Royal Holloway, University of London. MJ Fry is supported by a research grant from the School of Animal and Microbial Sciences, University of Reading. This research was initiated in the Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, Sutton, Surrey, UK with research support from GlaxoWellcome plc. (MR Crompton, T Kamalati, HE Jolin) and the Leopold Muller Trust (MJ Fry).

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Authors and Affiliations

  1. School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK

    M R Crompton

  2. CRC Laboratories, 5th floor MRC Cyclotron Building, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

    T Kamalati

  3. Medical Research Council Laboratory of Molecular Biology, MRC Centre Hills Road, Cambridge, CB2 2QH, UK

    H E Jolin

  4. School of Animal and Microbial Sciences, University of Reading, Whiteknights, PO Box 228, Reading, RG6 6AJ, UK

    M J Fry

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  1. T Kamalati
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Kamalati, T., Jolin, H., Fry, M. et al. Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation. Oncogene 19, 5471–5476 (2000). https://doi.org/10.1038/sj.onc.1203931

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