Abstract

Estrogen receptor (ER)-beta 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 (ER beta 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 ER beta, 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 ER beta agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ER beta-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma.

Autore Pugliese

• Valenti Daniela , Vacca Rosa Anna

Tutti gli autori

• Manente A.G.; Valenti D.; Pinton G.; Jithesh P.V.; Daga A.; Rossi L.; Gray S.G.; O'Byrne K.J.; Fennell D.A.; Vacca R.A.; Nilsson S.; Mutti L.; Moro L.

Titolo volume/Rivista

Oncogenesis

Anno di pubblicazione

2013

ISSN

2157-9024

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

Non Disponibile