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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

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

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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⟩
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