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 journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2172-84
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • 5' Untranslated Regions
  • Alternative Splicing
  • Blotting, Western
  • Breast Neoplasms
  • Cell Line, Tumor
  • Estrogen Receptor beta
  • Eukaryotic Initiation Factor-4E
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Neoplasms
  • Protein Biosynthesis
  • Protein Isoforms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis
  • Journal Article
  • Research Support, Non-U.S. Gov't

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

    Smith, L., Brannan, R. A., Hanby, A. M., Shaaban, A. M., Verghese, E. T., Peter, M. B., Pollock, S., Satheesha, S., Szynkiewicz, M., Speirs, V., & Hughes, T. A. (2010). Differential regulation of oestrogen receptor β isoforms by 5' untranslated regions in cancer. Journal of Cellular and Molecular Medicine, 14(8), 2172-84. https://doi.org/10.1111/j.1582-4934.2009.00867.x