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

Arcangela G. Manente, Giulia Pinton, Sara Zonca, Daniela Tavian, Tanwir Habib, Puthen V. Jithesh, Dean Fennell, Stefan Nilsson, Laura Moro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1227-1238
Number of pages12
JournalEpigenomics
Volume8
Issue number9
DOIs
Publication statusPublished - Sept 2016
Externally publishedYes

Keywords

  • ERβ
  • H3K27me3
  • KDM6B
  • epigenetic
  • human malignant pleural mesothelioma

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