Update on the therapeutic significance of estrogen receptor beta in malignant gliomas

Yu-Long Lan, Shuang Zou, Xun Wang, Jia-Cheng Lou, Jin-Shan Xing, Min Yu and Bo Zhang _

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Oncotarget. 2017; 8:81686-81696. https://doi.org/10.18632/oncotarget.20970

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Yu-Long Lan1,2,3,*, Shuang Zou3,4,*, Xun Wang1, Jia-Cheng Lou1, Jin-Shan Xing1, Min Yu5 and Bo Zhang1

1Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China

2Department of Pharmacy, Dalian Medical University, Dalian, 116044, China

3Department of Physiology, Dalian Medical University, Dalian, 116044, China

4Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

5Department of Neurology, The Third People’s Hospital of Dalian, Non-Directly Affiliated Hospital of Dalian Medical University, Dalian, 116033, China

*These authors contributed equally to this work

Correspondence to:

Bo Zhang, email: [email protected]

Min Yu, email: [email protected]

Keywords: estrogen receptor β, glioma, expression, therapy

Received: June 22, 2017     Accepted: August 29, 2017     Published: September 18, 2017


Malignant glioma is the most fatal of the astrocytic lineage tumors despite therapeutic advances. Men have a higher glioma incidence than women, indicating that estrogen level differences between men and women may influence glioma pathogenesis. However, the mechanism underlying the anticancer effects of estrogen has not been fully clarified and is complicated by the presence of several distinct estrogen receptor types and the identification of a growing number of estrogen receptor splice variants. Specifically, it is generally accepted that estrogen receptor alpha (ERα) functions as a tumor promoter, while estrogen receptor beta (ERβ) functions as a tumor suppressor, and the role and therapeutic significance of ERβ signaling in gliomas remains elusive. Thus, a deeper analysis of ERβ could elucidate the role of estrogens in gender-related cancer incidence. ERβ has been found to be involved in complex interactions with malignant gliomas. In addition, the prognostic value of ERβ expression in glioma patients should not be ignored when considering translating experimental findings to clinical practice. More importantly, several potential drugs consisting of selective ERβ agonists have exhibited anti-glioma activities and could further extend the therapeutic potential of ERβ-selective agonists. Here, we review the literature to clarify the anti-glioma effect of ERβ. To clarify ERβ-mediated treatment effects in malignant gliomas, this review focuses on the potential mechanisms mediated by ERβ in the intracellular signaling events in glioma cells, the prognostic value of ERβ expression in glioma patients, and various ERβ agonists that could be potential drugs with anti-glioma activities.

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