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Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis

Oncogene volume 27, pages 548–556 (2008)Cite this article

Abstract

The Src-associated substrate in mitosis Sam68 is a KH type RNA-binding protein known to be a substrate of numerous tyrosine kinases, and often referred to as a STAR (signal transduction activator of RNA) protein. Herein, we observed that Sam68-null mice display mammary gland and the uterine development defects. Moreover, we report that Sam68 haploinsufficiency impedes mammary tumor onset in vivo driven by the potent mammary-targeted polyoma middle T-antigen (MMTV-PyMT) oncogene. The effect was cell autonomous as the Sam68 knockdown in PyMT-transformed cell lines also delayed tumorigenesis and metastasis formation in nude mice. Interestingly, tumor extracts isolated from PyMT/Sam68+/− mice compared with PyMT/Sam68+/+ mice contained activated Src and FAK kinases. These findings suggest that Sam68 may be a modulator of tyrosine kinase activity in vivo and a signaling requirement for mammary tumorigenesis and metastasis.

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Acknowledgements

We thank Dr Robert D Cardiff (University of California-Davis) and Dr Stephen M Dilworth (Imperial College London, UK) for the generous gifts of PyMT-derived cells and antibody, respectively. This work was supported by Grant MT-13377 from the Canadian Institutes of Health Research (CIHR). MEH is the recipient of a postdoctoral fellowship from Cancer Research Society Inc. SR is an investigator of the CIHR.

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Authors and Affiliations

  1. Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montréal, Québec, Canada

    S Richard, G Vogel, M-É Huot, T Guo & K E Lukong

  2. Department of Medicine, McGill University, Montréal, Québec, Canada

    S Richard, G Vogel, M-É Huot, T Guo, W J Muller & K E Lukong

  3. Department of Oncology, McGill University, Montréal, Québec, Canada

    S Richard, G Vogel, M-É Huot, T Guo & K E Lukong

  4. Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada

    W J Muller

  5. Department of Biochemistry, McGill University, Montréal, Québec, Canada

    W J Muller

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  1. S Richard
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Correspondence to S Richard.

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Richard, S., Vogel, G., Huot, MÉ. et al. Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis. Oncogene 27, 548–556 (2008). https://doi.org/10.1038/sj.onc.1210652

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