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

Mol Cell Endocrinol. 2013 Aug 25;376(1-2):125-35. doi: 10.1016/j.mce.2013.06.023. Epub 2013 Jun 24.

Abstract

Estrogen receptor β (ERβ) and its isoforms have different putative functions and expression patterns in prostate cancer. Current studies on 5'-most exons, 0K and 0N, show that their respective promoters are actively involved in transcription. These data, however, do not explain why ERβ isoforms are differentially expressed in normal and cancerous tissues, since 0K and 0N transcripts are detectable in clinical specimens. Various combinations of 5' untranslated exons, termed exon 0Xs, associate with promoter 0K only and exon 0Xs accommodate upstream open reading frames (uORFs) reducing protein expression. Moreover, ERβ1, 2, and 5 are transcriptionally linked to promoter 0K; exon 0Xs are spliced only into ERβ2 and ERβ5 transcripts, suggesting that their expressions are regulated post-transcriptionally by exon 0Xs. This study reveals that expression of ERβ1 is regulated primarily at the transcriptional level, whereas that of ERβ2 and ERβ5 is controlled by the interplay between transcriptional and post-transcriptional regulation.

Keywords: 5′ Untranslated region; ERbeta2; ERbeta5; Post-transcriptional; Promoter; Upstream open reading frame.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5' Untranslated Regions
  • Cell Line, Tumor
  • Estrogen Receptor beta / genetics*
  • Estrogen Receptor beta / metabolism
  • Exons*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Open Reading Frames
  • Promoter Regions, Genetic*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Biosynthesis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Transcription, Genetic

Substances

  • 5' Untranslated Regions
  • Estrogen Receptor beta
  • Protein Isoforms