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Title: Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo
Authors: Manente, A. G.
Valenti, D.
Pinton, G.
Jithesh, P. V.
Daga, A.
Rossi, L.
Gray, S. G.
O'Byrne, K. J.
Fennell, Dean Anthony
Vacca, R. A.
Nilsson, S.
Mutti, L.
Moro, L.
First Published: 23-Sep-2013
Publisher: Nature Publishing Group
Citation: Oncogenesis, 2013, 2, e72
Abstract: Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma.
DOI Link: 10.1038/oncsis.2013.32
eISSN: 2157-9024
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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