Involvement of estrogen receptor β5 in the progression of glioma

Wenjun Li, Ali Winters, Ethan Poteet, Myoung Gwi Ryou, Song Lin, Shuyu Hao, Zhen Wu, Fang Yuan, Kimmo J. Hatanpaa, James W. Simpkins, Shao Hua Yang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Emerging evidence suggests a decline of ERβ expression in various peripheral cancers. ERβ has been proposed as a cancer brake that inhibits tumor proliferation. In the current study, we have identified ERβ5 as the predominant isoform of ERβ in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERβ transcription in U87 cells, suggesting elevated ERβ expression in glioma might be induced by the hypoxic stress in the tumor. Over-expression of either ERβ1 or ERβ5 increased PTEN expression and inhibited activation of the PI3K/AKT/mTOR pathway. In addition, ERβ5 inhibited the MAPK/ERK pathway. In U87 cells, ERβ1 and ERβ5 inhibit cell proliferation and reduced cells in the S+G2/M phase. Our findings suggest hypoxia induced ERβ5 expression in glioma as a self-protective mechanism against tumor proliferation and that ERβ5 might serve as a therapeutic target for the treatment of glioma.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalBrain Research
StatePublished - Mar 29 2013


  • Estrogen receptor β
  • Glioblastoma multiforme
  • Hypoxia inducible factor
  • PTEN

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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