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Therapeutic significance of estrogen receptor ? agonists in gliomas.

ABSTRACT: Gliomas are the most common and devastating central nervous system neoplasms. A gender bias exists in their development: females are at lower risk than males, implicating estrogen-mediated protective effects. Estrogen functions are mediated by two estrogen receptor (ER) subtypes: ER?, which functions as tumor promoter, and ER?, which functions as tumor suppressor. We examined the potential use of ER? agonists as a novel therapeutic to curb the growth of gliomas. Western analysis of six glioma model cells showed detectable expression of ER? with little or no ER?. Treatment of glioma cells with ER? agonists resulted in significant decrease in proliferation. Immunohistochemical analysis of tumor tissues revealed that ER? expression is downregulated in high-grade gliomas. We found that ER? agonists promote both expression and tumor-suppressive functions of ER? in glioma cells. Liquiritigenin, a plant-derived ER? agonist significantly reduced in vivo tumor growth in a xenograft model. Compared with control mice, animals treated with liquiritigenin had greater than 50% reduction in tumor volume and size. Immunohistochemical analysis of tumors revealed a significant increase in the nuclear ER? expression with a concomitant decrease in cell proliferation in the liquiritigenin-treated group. Our results suggest that ER? signaling has a tumor-suppressive function in gliomas. Because ER? agonists are currently in clinical trials and are well tolerated with fewer side effects, identification of an ER? agonist as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in glioma patients.

SUBMITTER: Sareddy GR

PROVIDER: S-EPMC3721065 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Therapeutic significance of estrogen receptor β agonists in gliomas.

Sareddy Gangadhara R GR Nair Binoj C BC Gonugunta Vijay K VK Zhang Quan-guang QG Brenner Andrew A Brann Darrell W DW Tekmal Rajeshwar Rao RR Vadlamudi Ratna K RK

Molecular cancer therapeutics 20120321 5

Gliomas are the most common and devastating central nervous system neoplasms. A gender bias exists in their development: females are at lower risk than males, implicating estrogen-mediated protective effects. Estrogen functions are mediated by two estrogen receptor (ER) subtypes: ERα, which functions as tumor promoter, and ERβ, which functions as tumor suppressor. We examined the potential use of ERβ agonists as a novel therapeutic to curb the growth of gliomas. Western analysis of six glioma mo ...[more]

PMID: 22442308

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Therapeutic significance of estrogen receptor ? agonists in gliomas.

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Therapeutic significance of estrogen receptor β agonists in gliomas.

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