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    Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer.

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    Authors
    Lundgren, K
    Nordenskjöld, B
    Landberg, Göran
    Affiliation
    Department of Laboratory Medicine, Center for Molecular Pathology, Malmö University Hospital, Lund University, Malmö SE-205 02, Sweden.
    Issue Date
    2009-11-17
    
    Metadata
    Show full item record
    Abstract
    BACKGROUND: Hypoxia is an element of the tumour microenvironment that impacts upon numerous cellular factors linked to clinical aggressiveness in cancer. One such factor, Snail, a master regulator of the epithelial-mesenchymal transition (EMT), has been implicated in key tumour biological processes such as invasion and metastasis. In this study we set out to investigate regulation of EMT in hypoxia, and the importance of Snail in cell migration and clinical outcome in breast cancer. METHODS: Four breast cancer cell lines were exposed to 0.1% oxygen and expression of EMT markers was monitored. The migratory ability was analysed following Snail overexpression and silencing. Snail expression was assessed in 500 tumour samples from premenopausal breast cancer patients, randomised to either 2 years of tamoxifen or no adjuvant treatment. RESULTS: Exposure to 0.1% oxygen resulted in elevated levels of Snail protein, along with changes in vimentin and E-cadherin expression, and in addition increased migration of MDA-MB-468 cells. Overexpression of Snail increased the motility of MCF-7, T-47D and MDA-MB-231 cells, whereas silencing of the protein resulted in decreased migratory propensity of MCF-7, MDA-MB-468 and MDA-MB-231 cells. Moreover, nuclear Snail expression was associated with tumours of higher grade and proliferation rate, but not with disease recurrence. Interestingly, Snail negativity was associated with impaired tamoxifen response (P=0.048). CONCLUSIONS: Our results demonstrate that hypoxia induces Snail expression but generally not a migratory phenotype, suggesting that hypoxic cells are only partially pushed towards EMT. Furthermore, our study supports the link between Snail and clinically relevant features and treatment response.
    Citation
    Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer. 2009, 101 (10):1769-81 Br. J. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/91621
    DOI
    10.1038/sj.bjc.6605369
    PubMed ID
    19844232
    Type
    Article
    Language
    en
    ISSN
    1532-1827
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.bjc.6605369
    Scopus Count
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    All Paterson Institute for Cancer Research

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