Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

Molecular characterization of the dual effect of the GPER agonist G-1 in glioblastoma

Résumé

Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio-chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM.

Fichier principal
Vignette du fichier
Hirtz 2022 bis.pdf (2.22 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-03876444 , version 1 (28-11-2022)

Licence

Identifiants

Citer

Alex Hirtz, Yann Bailly, Fabien Rech, Julien Pierson, Hélène Dumond, et al.. Molecular characterization of the dual effect of the GPER agonist G-1 in glioblastoma. International Journal of Molecular Sciences, 2022, 23 (22), pp.14309. ⟨10.3390/ijms232214309⟩. ⟨hal-03876444⟩
100 Consultations
145 Téléchargements

Altmetric

Partager

  • More