KDM6B histone demethylase is an epigenetic regulator of estrogen receptor β expression in human pleural mesothelioma

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.