1. KDM6B histone demethylase is an epigenetic regulator of estrogen receptor β expression in human pleural mesothelioma.
- Author
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Manente AG, Pinton G, Zonca S, Tavian D, Habib T, Jithesh PV, Fennell D, Nilsson S, and Moro L
- Subjects
- Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Hypoxia, Cell Line, Tumor, Estrogen Receptor beta metabolism, Histones metabolism, Humans, Jumonji Domain-Containing Histone Demethylases metabolism, Lung Neoplasms metabolism, Mesothelioma metabolism, Mesothelioma, Malignant, Methylation, Protein Processing, Post-Translational, Epigenesis, Genetic, Estrogen Receptor beta genetics, Jumonji Domain-Containing Histone Demethylases genetics, Lung Neoplasms genetics, Mesothelioma genetics
- 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.
- Published
- 2016
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