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, Shaohua Yang

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

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
Pages (from-to)97-107
Number of pages11
JournalBrain Research
Volume1503
DOIs
StatePublished - 29 Mar 2013

Fingerprint

Glioma
Estrogen Receptors
Neoplasms
MAP Kinase Signaling System
G2 Phase
Phosphatidylinositol 3-Kinases
Cell Division
Protein Isoforms
Cell Proliferation
Brain
Hypoxia
Therapeutics

Keywords

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

Cite this

Li, Wenjun ; Winters, Ali ; Poteet, Ethan ; Ryou, Myoung Gwi ; Lin, Song ; Hao, Shuyu ; Wu, Zhen ; Yuan, Fang ; Hatanpaa, Kimmo J. ; Simpkins, James W. ; Yang, Shaohua. / Involvement of estrogen receptor β5 in the progression of glioma. In: Brain Research. 2013 ; Vol. 1503. pp. 97-107.
@article{ea04322a96d941dca89157893d9f9293,
title = "Involvement of estrogen receptor β5 in the progression of glioma",
abstract = "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.",
keywords = "Estrogen receptor β, Glioblastoma multiforme, Hypoxia inducible factor, PTEN",
author = "Wenjun Li and Ali Winters and Ethan Poteet and Ryou, {Myoung Gwi} and Song Lin and Shuyu Hao and Zhen Wu and Fang Yuan and Hatanpaa, {Kimmo J.} and Simpkins, {James W.} and Shaohua Yang",
year = "2013",
month = "3",
day = "29",
doi = "10.1016/j.brainres.2013.02.004",
language = "English",
volume = "1503",
pages = "97--107",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

Li, W, Winters, A, Poteet, E, Ryou, MG, Lin, S, Hao, S, Wu, Z, Yuan, F, Hatanpaa, KJ, Simpkins, JW & Yang, S 2013, 'Involvement of estrogen receptor β5 in the progression of glioma', Brain Research, vol. 1503, pp. 97-107. https://doi.org/10.1016/j.brainres.2013.02.004

Involvement of estrogen receptor β5 in the progression of glioma. / Li, Wenjun; Winters, Ali; Poteet, Ethan; Ryou, Myoung Gwi; Lin, Song; Hao, Shuyu; Wu, Zhen; Yuan, Fang; Hatanpaa, Kimmo J.; Simpkins, James W.; Yang, Shaohua.

In: Brain Research, Vol. 1503, 29.03.2013, p. 97-107.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Involvement of estrogen receptor β5 in the progression of glioma

AU - Li, Wenjun

AU - Winters, Ali

AU - Poteet, Ethan

AU - Ryou, Myoung Gwi

AU - Lin, Song

AU - Hao, Shuyu

AU - Wu, Zhen

AU - Yuan, Fang

AU - Hatanpaa, Kimmo J.

AU - Simpkins, James W.

AU - Yang, Shaohua

PY - 2013/3/29

Y1 - 2013/3/29

N2 - 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.

AB - 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.

KW - Estrogen receptor β

KW - Glioblastoma multiforme

KW - Hypoxia inducible factor

KW - PTEN

UR - http://www.scopus.com/inward/record.url?scp=84875222587&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2013.02.004

DO - 10.1016/j.brainres.2013.02.004

M3 - Article

VL - 1503

SP - 97

EP - 107

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -

Li W, Winters A, Poteet E, Ryou MG, Lin S, Hao S et al. Involvement of estrogen receptor β5 in the progression of glioma. Brain Research. 2013 Mar 29;1503:97-107. https://doi.org/10.1016/j.brainres.2013.02.004