University of Hertfordshire Research Archive

        JavaScript is disabled for your browser. Some features of this site may not work without it.

        Browse

        All of UHRABy Issue DateAuthorsTitlesThis CollectionBy Issue DateAuthorsTitles

        Arkivum Files

        My Downloads
        View Item 
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item

        WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

        View/Open
        Final Accepted Version (PDF, 10Mb)
        Author
        Bisson, Isabelle
        Prowse, David M.
        Attention
        2299/16115
        Abstract
        Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.
        Publication date
        2009-06-01
        Published in
        Cell Research
        Published version
        https://doi.org/10.1038/cr.2009.43
        Other links
        http://hdl.handle.net/2299/16115
        Relations
        School of Life and Medical Sciences
        Metadata
        Show full item record
        Keep in touch

        © 2018 University of Hertfordshire

        I want to...

        • Apply for a course
        • Download a Prospectus
        • Find a job at the University
        • Make a complaint
        • Contact the Press Office

        Go to...

        • Accommodation booking
        • Your student record
        • Bayfordbury
        • KASPAR
        • UH Arts

        The small print

        • Terms of use
        • Privacy and cookies
        • Criminal Finances Act 2017
        • Modern Slavery Act 2015
        • Sitemap

        Find/Contact us

        • T: +44 (0)1707 284000
        • E: ask@herts.ac.uk
        • Where to find us
        • Parking
        • hr
        • qaa
        • stonewall
        • AMBA
        • ECU Race Charter
        • disability confident
        • AthenaSwan