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

Laura Smith1, Rebecca A Brannan, Andrew M Hanby

  • 1Leeds Institute of Molecular Medicine, Leeds University, Leeds, UK Department of Histopathology, St James's University Hospital, Leeds, UK.

Journal of Cellular and Molecular Medicine
|October 6, 2010
PubMed

Insights

Investigating human estrogen receptor beta (ERβ) 5' untranslated regions (UTRs) reveals novel regulatory mechanisms. These 5'UTRs control ERβ expression and isoform-specific function, impacting cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Estrogen receptors (ERs) are key in cancer biology.
  • Estrogen receptor beta (ERβ) function and regulation are poorly understood.
  • Discrepancies in ERβ mRNA and protein levels and multiple ERβ isoforms complicate research.

Purpose of the Study:

  • To investigate the role of human ERβ 5' untranslated regions (UTRs) in regulating ERβ expression and function.
  • To elucidate mechanisms underlying ERβ expression variability and isoform-specific control.

Main Methods:

  • Analysis of human ERβ 5'UTRs.
  • Investigation of translational regulation.
  • Examination of cellular context and carcinogenesis influences.
  • Identification of upstream open reading frames and RNA secondary structure contributions.

Main Results:

  • Two alternative ERβ 5'UTRs significantly and differentially influence ERβ expression at the translational level.
  • These effects are modulated by cellular context and during carcinogenesis.
  • Upstream open reading frames and RNA secondary structures contribute to ERβ regulation.
  • Mechanisms explaining ERβ mRNA-protein discrepancies were identified.
  • Novel mechanisms for differential regulation of ERβ isoforms (1, 2, and 5) via 5'UTRs were discovered.

Conclusions:

  • Human ERβ 5'UTRs are critical regulators of ERβ expression and function.
  • These regulatory mechanisms explain ERβ mRNA-protein non-concordance.
  • 5'UTRs provide the first described means for differential regulation of ERβ isoforms, impacting cancer biology.

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