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

作者：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^*

来源：Journal of Cellular and Molecular Medicine, 2010, 14(8): 2172-2184.

DOI：10.1111/j.1582-4934.2009.00867.x

• breast cancer
• ER beta
• 5'UTRs
• translation
• uORFs
• RNA structure
• alternative splicing

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

• 出版日期2010-8