Post-transcriptional regulation of gene expression by alternative 5'-untranslated regions in carcinogenesis.

Post-transcriptional regulation, via 5'-UTRs (5'-untranslated regions), plays an important role in the control of eukaryotic gene expression. Recent analyses of the mammalian transcriptome suggest that most of the genes express multiple alternative 5'-UTRs and inappropriate expression of these regions has been shown to contribute to the development of carcinogenesis. The present review will focus on the complex post-transcriptional regulation of ERbeta (oestrogen receptor beta) expression. In particular, results from our laboratory suggest that the expression of alternative 5'-UTRs plays a key role in determining the level of ERbeta protein expression. We have also shown that these alternative ERbeta 5'-UTRs have a tissue-specific distribution and are differentially expressed between various normal and tumour tissues. Our results also suggest that alternative 5'-UTRs can influence downstream splicing events, thereby perhaps affecting ERbeta function. These results suggest that alternative 5'-UTRs may have an overall influence on ER activity and this may have important implications for our understanding of cancer biology and treatment.