Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

INTRODUCTION:Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43) and estrogen receptors (ERs). Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we inve...

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Main Authors: Zahra Moinfar, Hannes Dambach, Bodo Schoenebeck, Eckart Förster, Nora Prochnow, Pedro Michael Faustmann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4769248?pdf=render
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author Zahra Moinfar
Hannes Dambach
Bodo Schoenebeck
Eckart Förster
Nora Prochnow
Pedro Michael Faustmann
author_facet Zahra Moinfar
Hannes Dambach
Bodo Schoenebeck
Eckart Förster
Nora Prochnow
Pedro Michael Faustmann
author_sort Zahra Moinfar
collection DOAJ
description INTRODUCTION:Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43) and estrogen receptors (ERs). Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2) on Cx43 expression in two glioma cell lines with variable native expression of Cx43. MATERIALS AND METHODS:F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique. RESULTS:E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells. DISCUSSION:These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.
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spelling doaj.art-0e04886c388d42bfb2d8690e4b64f0b82022-12-21T18:22:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e015000710.1371/journal.pone.0150007Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.Zahra MoinfarHannes DambachBodo SchoenebeckEckart FörsterNora ProchnowPedro Michael FaustmannINTRODUCTION:Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43) and estrogen receptors (ERs). Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2) on Cx43 expression in two glioma cell lines with variable native expression of Cx43. MATERIALS AND METHODS:F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique. RESULTS:E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells. DISCUSSION:These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.http://europepmc.org/articles/PMC4769248?pdf=render
spellingShingle Zahra Moinfar
Hannes Dambach
Bodo Schoenebeck
Eckart Förster
Nora Prochnow
Pedro Michael Faustmann
Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
PLoS ONE
title Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
title_full Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
title_fullStr Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
title_full_unstemmed Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
title_short Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
title_sort estradiol receptors regulate differential connexin 43 expression in f98 and c6 glioma cell lines
url http://europepmc.org/articles/PMC4769248?pdf=render
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AT bodoschoenebeck estradiolreceptorsregulatedifferentialconnexin43expressioninf98andc6gliomacelllines
AT eckartforster estradiolreceptorsregulatedifferentialconnexin43expressioninf98andc6gliomacelllines
AT noraprochnow estradiolreceptorsregulatedifferentialconnexin43expressioninf98andc6gliomacelllines
AT pedromichaelfaustmann estradiolreceptorsregulatedifferentialconnexin43expressioninf98andc6gliomacelllines