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Int. J. Mol. Sci. 2018, 19(2), 411; https://doi.org/10.3390/ijms19020411

Natural Anti-Estrogen Receptor Alpha Antibodies Able to Induce Estrogenic Responses in Breast Cancer Cells: Hypotheses Concerning Their Mechanisms of Action and Emergence

Laboratoire de Cancérologie Mammaire, Institut J. Bordet, Centre des Tumeurs de l’Université Libre de Bruxelles, 1, rue Héger-Bordet, 1000 Brussels, Belgium
This paper may be considered as a tribute to my colleague Albert Borkowski, Internist and Director of the Endocrinology Laboratory of the Institute J. Bordet, who passed away in 2007 and who first described certain biological functions of these antibodies.
Received: 25 December 2017 / Revised: 24 January 2018 / Accepted: 25 January 2018 / Published: 30 January 2018
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action)
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Abstract

The detection of human anti-estrogen receptor α antibodies (ERαABs) inducing estrogenic responses in MCF-7 mammary tumor cells suggests their implication in breast cancer emergence and/or evolution. A recent report revealing a correlation between the titer of such antibodies in sera from patients suffering from this disease and the percentage of proliferative cells in samples taken from their tumors supports this concept. Complementary evidence of the ability of ERαABs to interact with an epitope localized within the estradiol-binding core of ERα also argues in its favor. This epitope is indeed inserted in a regulatory platform implicated in ERα-initiated signal transduction pathways and transcriptions. According to some experimental observations, two auto-immune reactions may already be advocated to explain the emergence of ERαABs: one involving probably the idiotypic network to produce antibodies acting as estrogenic secretions and the other based on antibodies able to abrogate the action of a natural ERα inhibitor or to prevent the competitive inhibitory potency of released receptor degradation products able to entrap circulating estrogens and co-activators. All of this information, the aspect of which is mainly fundamental, may open new ways in the current tendency to combine immunological and endocrine approaches for the management of breast cancer. View Full-Text
Keywords: estrogen receptor α; natural antibodies; estrogenic responses; mechanism of action; auto-immune diseases estrogen receptor α; natural antibodies; estrogenic responses; mechanism of action; auto-immune diseases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Leclercq, G. Natural Anti-Estrogen Receptor Alpha Antibodies Able to Induce Estrogenic Responses in Breast Cancer Cells: Hypotheses Concerning Their Mechanisms of Action and Emergence. Int. J. Mol. Sci. 2018, 19, 411.

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