Differential expression of estrogen receptor beta isoforms in prostate cancer through interplay between transcriptional and translational regulation

Estrogen receptor beta (ER beta) and its isoforms have different putative functions and expression patterns in prostate cancer. Current studies on 5'-most exons, OK and ON, show that their respective promoters are actively involved in transcription. These data, however, do not explain why ER beta isoforms are differentially expressed in normal and cancerous tissues, since OK and ON transcripts are detectable in clinical specimens. Various combinations of 5' untranslated exons, termed exon OXs, associate with promoter OK only and exon OXs accommodate upstream open reading frames (uORFs) reducing protein expression. Moreover, ER beta 1, 2, and 5 are transcriptionally linked to promoter OK; exon OXs are spliced only into ER beta 2 and ER beta 5 transcripts, suggesting that their expressions are regulated post-transcriptionally by exon OXs. This study reveals that expression of ER beta 1 is regulated primarily at the transcriptional level, whereas that of ER beta 2 and ER beta 5 is controlled by the interplay between transcriptional and post-transcriptional regulation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.