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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2018

Open Access 01-12-2018 | Research

Membrane-bound estrogen receptor alpha initiated signaling is dynamin dependent in breast cancer cells

Authors: Istvan Marczell, Petra Balogh, Gabor Nyiro, Anna L. Kiss, Balazs Kovacs, Gabor Bekesi, Karoly Racz, Attila Patocs

Published in: European Journal of Medical Research | Issue 1/2018

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Abstract

Background

Although membrane-associated estrogen receptors (mERs) have been known to play important role in steroid-induced signal transmission, we still know little about their function in the estrogen-induced proliferation of breast cancer cells.

Methods

In our current work we tried to separate membrane-initiated estrogen receptor signaling from the overall estrogenic effect in MCF-7 breast carcinoma cells. Re-analyzing expression data from multiple microarray experiments, we selected a set of key regulatory genes involved in proliferation regulation and estrogen signaling to monitor estrogen-induced transcription changes. We then compared these expression changes after 17β-estradiol and a membrane receptor selective estrogen–BSA treatment using quantitative real-time PCR. In order to follow receptor trafficking we used light and electron microscopy.

Results

Our quantitative real-time PCR results confirmed that the selective membrane receptor agonist, estrogen–BSA induces similarly pronounced expression changes regarding these genes as 17β-estradiol. Morphological study revealed that the membrane-bound form of classical estrogen receptor alpha is internalized after ligand binding via dynamin-dependent, caveola-mediated endocytosis. Inhibition of this internalization with dynamin inhibitor, dynasore practically abolished the regulatory effect of E2-BSA, suggesting that interaction and internalization with the scaffold protein is necessary for effective signaling.

Conclusions

The physiological role of plasma membrane estrogen receptor alpha is intensively studied, yet there are still several aspects of it to be resolved. The dynamin-dependent, ligand-mediated internalization of mERs seems to play an important role in estrogen signaling. Our results may serve as another example of how membrane initiated estrogen signaling and nuclear receptor initiated signaling overlap and form an intertwined system. 
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Metadata
Title
Membrane-bound estrogen receptor alpha initiated signaling is dynamin dependent in breast cancer cells
Authors
Istvan Marczell
Petra Balogh
Gabor Nyiro
Anna L. Kiss
Balazs Kovacs
Gabor Bekesi
Karoly Racz
Attila Patocs
Publication date
01-12-2018
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2018
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-018-0328-7

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