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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.05.2014 | Original Article - Cancer Research

GPER functions as a tumor suppressor in triple-negative breast cancer cells

verfasst von: Christine Weißenborn, Tanja Ignatov, Hans-Joachim Ochel, Serban Dan Costa, Ana Claudia Zenclussen, Zoya Ignatova, Atanas Ignatov

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 5/2014

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Abstract

Background

The orphan, membrane-bound estrogen receptor (GPER) is expressed at high levels in a large fraction of breast cancer patients and its expression is favorable for patients’ survival.

Methods

We investigated the role of GPER as a potential tumor suppressor in triple-negative breast cancer cells MDA-MB-231 and MDA-MB-468 using cell cycle analysis and apoptosis assay. The constitutive activity of GPER was investigated.

Results

GPER-specific activation with G-1 agonist inhibited breast cancer cell growth in concentration-dependent manner via induction of the cell cycle arrest in G2/M phase, enhanced phosphorylation of histone H3 and caspase-3-mediated apoptosis. Analysis of the methylation status of the GPER promoter in the triple-negative breast cancer cells and in tissues derived from breast cancer patients revealed that GPER amount is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Furthermore, GPER expression was induced by stress factors, such as radiation, and GPER amount inversely correlated with the p53 expression level.

Conclusions

Overall, our results establish the protective role in breast cancer tumorigenesis, and the cell surface expression of GPER makes it an excellent potential therapeutic target for triple-negative breast cancer.

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Titel: GPER functions as a tumor suppressor in triple-negative breast cancer cells
verfasst von: Christine Weißenborn
Tanja Ignatov
Hans-Joachim Ochel
Serban Dan Costa
Ana Claudia Zenclussen
Zoya Ignatova
Atanas Ignatov
Publikationsdatum: 01.05.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 5/2014
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1620-8

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GPER functions as a tumor suppressor in triple-negative breast cancer cells