Identification and characterization of estrogen receptor-related receptor alpha and gamma in human glioma and astrocytoma cells

Abstract

The purpose of this study was to examine expression and function of estrogen receptor-related receptors (ERRs) in human glioma and astrocytoma cell lines. These estrogen receptor-negative cell lines expressed ERRα and ERRγ proteins to varying degree in a cell context dependent manner, with U87MG glioma cells expressing both orphan nuclear receptors. Cell proliferation assays were performed in the presence of ERR isoform-specific agonists and antagonists, and the calculated EC50 and IC50 values were consistent with previous reported values determined in other types of cancer cell lines. Induction of luciferase expression under the control of ERR isoform-specific promoters was also observed in these cells. These results indicate that ERRα and ERRγ are differentially expressed in these tumor cell lines and likely contribute to agonist-dependent ERR transcriptional activity.

MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

“…Given the crucial role of ESRRA in the regulation of energy metabolism, it is not surprising that it can accelerate cancer cell proliferation. Until now, many reports have suggested its potential involvement in the regulation of cancer cell proliferation (11)(12)(13)(14). Additionally, Wu et al (45) have demonstrated that an inverse agonist of ESRRA, XCT-790, can also induce cell death in a multidrug resistance cell line HepG2 (human liver hepatocellular carcinoma cell line).…”

“…More importantly, an increased level of ESRRA is linked to poor prognosis of breast, ovarian, and prostate tumors (7,9,10). Several reports suggest that the pharmacological modulation of ESRRA activity with specific inverse agonists such as XCT790 reduces proliferation of cell lines derived from breast, glial, lung, and cervical tumors (11)(12)(13)(14). Using the transwell assay, Zhao et al (15) have shown that ESRRA promotes cancer cell migration and invasion.…”

Do Steroid Hormones Play a Role in the Etiology of Glioma?

“…Since the 1980s, several investigators have attempted to identify steroid hormone receptors in normal human brain cells and in human glioma and glioblastoma cells, as well as in rat glial and glioma cell lines (42)(43)(44)(45)(46)(47)(48)(49)(50)(51). Classical ERs and/or progestin, glucocorticoid, and androgen receptors are expressed in normal rat glial cells (26,42).…”

“…Genistein, an isoflavone that binds preferentially to ERβ and that also inhibits protein tyrosine kinases and topoisomerase II, rapidly inhibited DNA synthesis in human glioma cells in a concentration-dependent manner (71). The SERM tamoxifen, which can have both estrogenic and antiestrogenic effects, also inhibits glioma cell proliferation and induces apoptosis in vitro (51,(72)(73)(74). Interestingly, both tamoxifen and a benzopyranone with SERM activity, CC-8490, have been reported to induce apoptosis in vitro and in vivo in ER-negative glioma cells (75).…”

“…Tamoxifen seems to be a pure antagonist for ERβ acting on EREs in the promoters of target genes but can have agonist activity on ERβ when the response is mediated by non-ERE mechanisms (77). Another possibility is that ER-related proteins may be expressed in gliomas and may mediate the response to tamoxifen (51). Finally, especially at high doses, tamoxifen might act independently of any steroid receptor by influencing calmodulin (78), various kinases (70), or intracellular calcium (79), or through other mechanisms (80).…”