Arcangela G Manente1, Giulia Pinton, Sara Zonca1, Daniela Tavian2, Tanwir Habib3, Puthen V Jithesh3, Dean Fennell4, Stefan Nilsson5, Laura Moro1. 1. Department of Pharmaceutical Sciences, University of Piemonte Orientale, Lgo Donegani 2, 28100 Novara, Italy. 2. Laboratory of Cellular Biochemistry & Molecular Biology, CRIBENS, Catholic University of the Sacred Heart, 20145 Milan, Italy. 3. Sidra Medical & Research Center, P.O. Box 26999 Doha, Qatar. 4. University of Leicester & Leicester University Hospitals, LE1 9HN, Leicester, UK. 5. Department of Biosciences & Nutrition, Karolinska Institutet, S-141 57 Huddinge, Sweden.
Abstract
AIM: To assess the correlation between KDM6B and estrogen receptor β (ERβ) expression in malignant pleural mesothelioma (MPM). MATERIALS & METHODS: We evaluated gene expression by in silico analysis of microarray data, real-time PCR and western blot in MPM tumors and cell lines. RESULTS & CONCLUSION: We report a strong positive correlation between the expression of KDM6B and ERβ in MPM tumors and cell lines. We describe that, in hypoxia, the HIF2α-KDM6B axis induces an epithelioid morphology and ERβ expression in biphasic MPM cells with estrogen receptor-negative phenotype. Reduced histone H3K27 tri-methylation confirms KDM6B activity under hypoxic conditions. Importantly, cells treated during reoxygenation with the selective ERβ agonist, KB9520, maintain ERβ expression and the less aggressive phenotype acquired in hypoxia.
AIM: To assess the correlation between KDM6B and estrogen receptor β (ERβ) expression in malignant pleural mesothelioma (MPM). MATERIALS & METHODS: We evaluated gene expression by in silico analysis of microarray data, real-time PCR and western blot in MPM tumors and cell lines. RESULTS & CONCLUSION: We report a strong positive correlation between the expression of KDM6B and ERβ in MPM tumors and cell lines. We describe that, in hypoxia, the HIF2α-KDM6B axis induces an epithelioid morphology and ERβ expression in biphasic MPM cells with estrogen receptor-negative phenotype. Reduced histone H3K27 tri-methylation confirms KDM6B activity under hypoxic conditions. Importantly, cells treated during reoxygenation with the selective ERβ agonist, KB9520, maintain ERβ expression and the less aggressive phenotype acquired in hypoxia.
Entities:
Keywords:
ERβ; H3K27me3; KDM6B; epigenetic; human malignant pleural mesothelioma
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