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Open Access 01-12-2013 | Research

GPER-1 acts as a tumor suppressor in ovarian cancer

Authors: Tanja Ignatov, Saskia Modl, Maike Thulig, Christine Weißenborn, Oliver Treeck, Olaf Ortmann, AC Zenclussen, Serban Dan Costa, Thomas Kalinski, Atanas Ignatov

Published in: Journal of Ovarian Research | Issue 1/2013

Abstract

Background

It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells.

Patients and methods

GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth.

Results

GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3.

Conclusion

GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer.

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Title: GPER-1 acts as a tumor suppressor in ovarian cancer
Authors: Tanja Ignatov
Saskia Modl
Maike Thulig
Christine Weißenborn
Oliver Treeck
Olaf Ortmann
AC Zenclussen
Serban Dan Costa
Thomas Kalinski
Atanas Ignatov
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-6-51

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GPER-1 acts as a tumor suppressor in ovarian cancer

Abstract

Background

Patients and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Patients and methods

Results

Conclusion

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