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    Stromal expression of β-arrestin-1 predicts clinical outcome and tamoxifen response in breast cancer.

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    Authors
    Lundgren, Katja L
    Tobin, Nicholas P
    Lehn, Sophie
    Stål, O
    Rydén, L
    Jirström, K
    Landberg, Göran
    Affiliation
    Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden.
    Issue Date
    2011-05
    
    Metadata
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    Abstract
    The G-protein coupled receptor associated protein β-arrestin-1 is crucial for the regulation of numerous biological processes involved in cancer progression, such as intracellular signaling and cell motility. The encoding gene ARRB1 is harbored in the same chromosomal region as the CCND1 gene (11q13). Amplification of CCND1, frequently encountered in breast cancer, often involves coamplification of additional oncogenes, as well as deletion of distal 11q genes. We investigated the clinical relevance of β-arrestin-1 in breast cancer and elucidated a potential link between β-arrestin-1 expression and CCND1 amplification. β-Arrestin-1 protein expression was evaluated in two breast cancer patient cohorts, comprising 179 patients (cohort I) and 500 patients randomized to either tamoxifen or no adjuvant treatment (cohort II). Additionally, migration after β-arrestin-1 overexpression or silencing was monitored in two breast cancer cell lines. Overexpression of β-arrestin-1 reduced the migratory propensity of both cell lines, whereas silencing increased migration. In cohort I, high expression of stromal β-arrestin-1 was linked to reduced patient survival, whereas in cohort II both high and absent stromal expression predicted a poor clinical outcome. Patients exhibiting low or moderate levels of stromal β-arrestin-1 did not benefit from tamoxifen, in contrast to patients exhibiting absent or high expression. Furthermore, CCND1 amplification was inversely correlated with tumor cell expression of β-arrestin-1, indicating ARRB1 gene deletion in CCND1-amplified breast cancers.
    Citation
    Stromal expression of β-arrestin-1 predicts clinical outcome and tamoxifen response in breast cancer. 2011, 13 (3):340-51 J Mol Diagn
    Journal
    Journal of Molecular Diagnostics
    URI
    http://hdl.handle.net/10541/201097
    DOI
    10.1016/j.jmoldx.2011.01.009
    PubMed ID
    21497294
    Type
    Article
    Language
    en
    ISSN
    1943-7811
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jmoldx.2011.01.009
    Scopus Count
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    All Paterson Institute for Cancer Research

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