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Tyrosine phosphatase PTPα contributes to HER2-evoked breast tumor initiation and maintenance

Oncogene volume 33, pages 398–402 (2014)Cite this article

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Abstract

Protein tyrosine phosphatase alpha (PTPα/PTPRA) was shown previously to be overexpressed in human primary breast cancers, and to suppress apoptosis in estrogen receptor-negative breast cancer cells in vitro. However, it is not known whether PTPα is important for mammary tumor initiation, maintenance and/or progression. We have used a combination of three-dimensional cultures, a transgenic mouse model of breast cancer lacking PTPα as well as xenografts of human breast cancer cell lines to address these questions. We found that PTPα knockdown after overt tumor development reduced the growth of HER2-positive human breast cancer cell lines, and that this effect was accompanied by a reduction in AKT phosphorylation. However, PTPα knockdown did not affect invasiveness of HER2-positive human breast cancer cells grown in three-dimensional cultures. Moreover, in MMTV-NeuNT/PTPα−/− mice, PTPα ablation did not affect NeuNT-evoked tumor onset or metastasis but decreased the number of tumors per mouse. Thus, we demonstrate that PTPα contributes to both HER2/Neu-mediated mammary tumor initiation and maintenance. Our results suggest that inhibition of PTPα can have a beneficial effect on HER2-positive breast cancers, but that inhibition of additional targets is needed to block breast tumorigenesis.

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Acknowledgements

We thank members of the Bentires-Alj laboratory for advice and discussions. Research in the laboratory of MBA is supported by the Novartis Research Foundation, the European Research Council (ERC starting grant 243211-PTPsBDC), the Swiss Cancer League and the Krebsliga Beider Basel.

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Author notes

  1. D S Meyer

    Present address: 4Current address: University of California San Francisco (UCSF), School of Medicine, Helen Diller Family Comprehensive Cancer Center, San Francisco, USA.,

  2. N Aceto

    Present address: 5Current address: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.,

  3. D S Meyer and N Aceto: These authors contributed equally to this work.

Authors and Affiliations

  1. Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland

    D S Meyer, N Aceto, N Sausgruber, H Brinkhaus, U Müller & M Bentires-Alj

  2. Department of Pediatrics and Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada

    C J Pallen

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  1. D S Meyer
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  2. N Aceto
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  3. N Sausgruber
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  4. H Brinkhaus
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  5. U Müller
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Correspondence to M Bentires-Alj.

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Meyer, D., Aceto, N., Sausgruber, N. et al. Tyrosine phosphatase PTPα contributes to HER2-evoked breast tumor initiation and maintenance. Oncogene 33, 398–402 (2014). https://doi.org/10.1038/onc.2012.585

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  • DOI: https://doi.org/10.1038/onc.2012.585

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