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Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation

Oncogene volume 22, pages 5006–5010 (2003)Cite this article

Abstract

Brk (PTK6) is a nonreceptor protein tyrosine kinase, which is expressed in over 60% of breast carcinoma tissue samples and breast tumour cell lines, but not normal mammary tissue or benign lesions. Since experimental Brk expression in nontransformed mammary epithelial cells enhances their mitogenic response to epidermal growth factor, it was important to determine the role Brk plays in the proliferation of breast carcinoma cells and validate it as a therapeutic target. We have used RNA interference to efficiently and specifically downregulate Brk protein levels in breast carcinoma cells, and determined that this results in a significant suppression of their proliferation. Additionally, through the expression of a kinase-inactive mutant, we have determined that Brk can mediate promotion of proliferation via a kinase-independent mechanism, potentially functioning as an ‘adapter’. These data identify Brk as a novel target for antiproliferative therapy in the majority of breast cancers, and illustrate the power of RNA interference for rapidly validating candidate therapeutic targets.

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Acknowledgements

We thank Dr Michael Fry, University of Reading, for helpful comments. AJH was supported by a grant from the Association for International Cancer Research.

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

    Amanda J Harvey & Mark R Crompton

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  1. Amanda J Harvey
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Correspondence to Mark R Crompton.

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Harvey, A., Crompton, M. Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation. Oncogene 22, 5006–5010 (2003). https://doi.org/10.1038/sj.onc.1206577

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