Estrogen receptor β: Potential target for therapy in adult granulosa cell tumors?

Alessandra Ciucci, Gabriella Ferrandina, Floriana Mascilini, Flavia Filippetti, Giovanni Scambia, Gian Franco Zannoni, Daniela Gallo

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Adult granulosa cell tumor (AGCT) is a rare form of sex-cord stromal ovarian tumors. Due to their origin, AGCTs secrete estrogens, and thus, estrogen receptor (ER)-mediated signaling has been considered as a possible target for therapy. The aim of the present study was to get insights into estrogen receptor status and activity in AGCTs, as a strategy to provide molecular support for personalized hormonal treatments. Methods: We evaluated by immunohistochemistry the expression of ERα, ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) in 20 untreated AGCTs and 12 unmatched recurrent lesions. Thereafter, we visualized by immunofluorescence, the subcellular distribution of cytoplasmic receptors, and by the proximity ligation assays (PLA) we characterized in situ their ability to interact with other proteins involved in the apoptotic cascade. Results: Primary AGCTs predominantly expressed ERβ isoforms, along with PR and AR, while only 30% of patients showed ERα expression. Recurrent tumors were associated with a decrease in AR levels. From mechanistic studies it emerges that ERβ2, and to a lesser extent ERβ1 and AR, are mitochondrial components in cancer cells and that ERβ2 can act as a binding partner of proteins involved in the apoptotic cascade, in turn potentially inhibiting apoptosis. Conclusions: As in other endocrine tumors, ERβ may play a role in the pathogenesis of AGCT; it is crucial to understand estrogen receptor-mediated pathways before planning hormonal treatment strategies in AGCT.

Original languageEnglish
Pages (from-to)158-165
Number of pages8
JournalGynecologic Oncology
Volume150
Issue number1
DOIs
Publication statusPublished - Jul 1 2018

Keywords

  • ERβ
  • Estradiol
  • Hormonal therapy
  • Mitochondria
  • Ovary
  • Personalized medicine

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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