Differential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer

Laura Smith, Rebecca A. Brannan, Andrew M. Hanby, Abeer M. Shaaban, Eldo T. Verghese, Mark B. Peter, Steven Pollock, Sampoorna Satheesha, Marcin Szynkiewicz, Valerie Speirs, Thomas A. Hughes

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Oestrogen receptors (ERs) are critical regulators of the behaviour of many cancers. Despite this, the roles and regulation of one of the two known ERs - ERβ- are poorly understood. This is partly because analyses have been confused by discrepancies between ERβ expression at mRNA and proteins levels, and because ERβ is expressed as several functionally distinct isoforms. We investigated human ERβ 5′ untranslated regions (UTRs) and their influences on ERβ expression and function. We demonstrate that two alternative ERβ 5′UTRs have potent and differential influences on expression acting at the level of translation. We show that their influences are modulated by cellular context and in carcinogenesis, and demonstrate the contributions of both upstream open reading frames and RNA secondary structure. These regulatory mechanisms offer explanations for the non-concordance of ERβ mRNA and protein. Importantly, we also demonstrate that 5′UTRs allow the first reported mechanisms for differential regulation of the expression of the ERβ isoforms 1, 2 and 5, and thereby have critical influences on ERβ function. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
    Original languageEnglish
    Pages (from-to)2172-2184
    Number of pages12
    JournalJournal of cellular and molecular medicine
    Volume14
    Issue number8
    Publication statusPublished - Aug 2010

    Keywords

    • 5′UTRs
    • Alternative splicing
    • Breast cancer
    • ERβ
    • RNA structure
    • Translation
    • UORFs

    Fingerprint

    Dive into the research topics of 'Differential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer'. Together they form a unique fingerprint.

    Cite this