The role of oestrogens in ovarian cancer
GCT is a rare form of malignancy that accounts for about 5 % of ovarian tumours. Although it can occur in women of all ages, younger patients with GCT have better prognosis when compared to older patients. Most GCT patients have elevated secretion of sex steroid oestrogens, among which 17 beta-oestradiol (E2) is found elevated in approximately 70 % of patients. Scientists of the EU-funded ESTROVARYTUMOUR (Investigating the roles and mechanisms of action of oestrogens via oestrogen receptor ß in granulosa cell tumours of the ovary) project investigated the impact of oestrogens and their mechanisms of action in GCT growth and progression. Molecular studies were performed on two human oestrogen receptor (ER)-positive GCT-derived cell lines. Treatment with E2 appears to be beneficial for patients with advanced GCT as it seems to prevent metastatic granulosa cell migration. Scientists discovered that E2 represses ERK1/2 signalling in a non-genomic, transcription-independent manner through the GPER-1 receptor. Scientists used immunocompromised animals to engraft human GCT cells in a mouse model. These models allow the investigation, including the in vivo imaging, of the protective effects of oestradiol or GPER-1 agonists on GCT progression and metastasis. The ESTROVARYTUMOUR study provided very important knowledge on the role of oestrogens in GCT development and created the basis for the in vivo stage in the investigation. Importantly, in this particular form of ovarian cancer, E2 treatment may well prevent further metastasis. The generated information could find immediate clinical applicability for the benefit of patients with GCT.
Keywords
Oestrogen, ovarian cancer, granulosa cell tumour, 17-beta oestradiol, ESTROVARYTUMOUR, GPER-1
