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    Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer

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    Publication date
    2013
    Author
    Mathew, G.
    Mitchell, Andrew
    Down, J.M.
    Jacobs, L.A.
    Hamdy, F.C.
    Eaton, C.
    Rosario, D.J.
    Cross, S.S.
    Winder, S.J.
    Keyword
    Androgens
    ; Cell Line
    ; Cell nucleus
    ; Dystroglycans
    ; Gene expression regulation
    ; Humans
    ; Immunohistochemistry
    ; Male
    ; Myristic acid
    ; Oligonucleotide array sequence analysis
    ; Phosphorylation
    ; Phosphotyrosine
    ; Prostate
    ; Prostatic neoplasms
    ; Protein transport
    ; Transcription factors
    ; Transcription
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    Abstract
    Dystroglycan is frequently lost in adenocarcinoma, but the mechanisms and consequences are poorly understood. We report an analysis of beta-dystroglycan in prostate cancer in human tissue samples and in LNCaP cells in vitro. There is progressive loss of beta-dystroglycan immunoreactivity from basal and lateral surfaces of prostate epithelia which correlates significantly with increasing Gleason grade. In about half of matched bone metastases there is significant dystroglycan re-expression. In tumour tissue and in LNCaP cells there is also a tyrosine phosphorylation-dependent translocation of beta-dystroglycan to the nucleus. Analysis of gene expression data by microarray, reveals that nuclear targeting of beta-dystroglycan in LNCaP cells alters the transcription of relatively few genes, the most unregulated being the transcription factor ETV1. These data suggest that proteolysis, tyrosine phosphorylation and translocation of dystroglycan to the nucleus resulting in altered gene transcription could be important mechanisms in the progression of prostate cancer.
    URI
    http://hdl.handle.net/10454/9555
    Citation
    Mathew G, Mitchell A, Down JM et al (2013) Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer. Scientific Reports, 3. Article Number 2792.
    Link to publisher’s version
    http://dx.doi.org/10.1038/srep02792
    Type
    Article
    Collections
    Life Sciences Publications

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