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Context-dependent role of Grb7 in HER2+ve and triple-negative breast cancer cell lines

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Abstract

Grb7 is an adapter protein, aberrantly co-overexpressed with HER2 and identified as an independent prognostic marker in breast cancer. It has been established that Grb7 exacerbates the cellular growth and migratory behaviour of HER2+ve breast cancer cells. Less is known about Grb7’s role in the context of HER2−ve cells. Here we directly compare the effect of stable Grb7 knockdown in oestrogen sensitive (T47D), HER2+ve (SKBR3) and triple-negative (MDA-MB-468 and MDA-MB-231) breast cancer cell lines on anchorage dependent and independent cell growth, wound healing and chemotaxis. All cell lines showed reduced ability to migrate upon Grb7 knockdown, despite their greatly varied endogenous levels of Grb7. Decreased cell proliferation was not observed in any of the cell lines upon Grb7 knockdown; however, decreased ability to form colonies was observed for all but the oestrogen sensitive cell line, depending upon the stringency of the growth conditions. The data reveal that Grb7 plays an important role in breast cancer progression, beyond the context of HER2+ve cell types.

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Acknowledgments

We thank Monash Micro Imaging for assistance with live cell microscopy and imaging, and Monash Flowcore for assistance with FACS.

Conflict of interest

The authors declare they have no conflicts of interest.

Funding

This work was supported by the National Health and Medical Research Council of Australia [APP1004332 awarded to JAW and JP] and National Health and Medical Research Council of Australia RD Wright Fellowship [#395525 awarded to JP].

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, VIC, 3800, Australia

    Reece C. C. Lim, John T. Price & Jacqueline A. Wilce

  2. College of Health and Biomedicine, Victoria University, St Albans, VIC, 3021, Australia

    John T. Price

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  1. Reece C. C. Lim
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Correspondence to Jacqueline A. Wilce.

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Lim, R.C.C., Price, J.T. & Wilce, J.A. Context-dependent role of Grb7 in HER2+ve and triple-negative breast cancer cell lines. Breast Cancer Res Treat 143, 593–603 (2014). https://doi.org/10.1007/s10549-014-2838-5

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  • DOI: https://doi.org/10.1007/s10549-014-2838-5

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