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

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 - ER?- are poorly understood. This is partly because analyses have been confused by discrepancies between ER? expression at mRNA and proteins levels, and because ER? is expressed as several functionally distinct isoforms. We investigated human ER? 5' untranslated regions (UTRs) and their influences on ER? expression and function. We demonstrate that two alternative ER? 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 ER? mRNA and protein. Importantly, we also demonstrate that 5'UTRs allow the first reported mechanisms for differential regulation of the expression of the ER? isoforms 1, 2 and 5, and thereby have critical influences on ER? function.

SUBMITTER: Smith L 

PROVIDER: S-EPMC3823008 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature