title: Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-Universität Bochum, 44801, Bochum, Germany.|International Graduate School of Neuroscience (IGSN), Ruhr-Universität Bochum, 44801, Bochum, Germany.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Moinfar
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-Universität Bochum, 44801, Bochum, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Dambach
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-Universität Bochum, 44801, Bochum, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Schoenebeck
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-Universität Bochum, 44801, Bochum, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Förster
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-Universität Bochum, 44801, Bochum, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Prochnow
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-Universität Bochum, 44801, Bochum, Germany.|International Graduate School of Neuroscience (IGSN), Ruhr-Universität Bochum, 44801, Bochum, Germany.
authors.forename: Pedro Michael
authors.initials: PM
authors.lastname: Faustmann
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D065171:Estrogen Receptor Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol