Open AccessDifferential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer
Author(s) -
Smith Laura,
Brannan Rebecca A.,
Hanby Andrew M.,
Shaaban Abeer M.,
Verghese Eldo T.,
Peter Mark B.,
Pollock Steven,
Satheesha Sampoorna,
Szynkiewicz Marcin,
Speirs Valerie,
Hughes Thomas A.
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00867.x
Subject(s) - gene isoform , untranslated region , upstream open reading frame , biology , three prime untranslated region , context (archaeology) , messenger rna , function (biology) , carcinogenesis , microbiology and biotechnology , translation (biology) , regulation of gene expression , genetics , cancer , gene , paleontology
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.