Oestradiol reduces liver receptor homolog-1 mRNA transcript stability in breast cancer cell lines

Kyren Lazarus, Zhe Zhao, Kevin Christopher Knower, Sarah Quynh Giao To, Ashwini L Chand, Colin Clyne

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E2), with LRH-1 mRNA transcript levels higher in oestrogen receptor alpha (ERalpha) positive (ER+) breast cancer cells compared to ER- cells. However, the presence of LRH-1 protein in ER- cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER- breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER- compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E2, showed increased mRNA stability in ER- versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E2 treatment, this effect mediated by ERalpha. Our data demonstrates that in ER- cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER- cells as well as ER- tumors suggests a possible role in the development of ER- tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER- and ER+ breast cancer.
Original languageEnglish
Pages (from-to)533 - 539
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume438
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • Liver Receptor Homolog-1
  • Oestrogen receptor alpha
  • mRNA stability

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