The estrogen receptor alpha-derived peptide ER alpha 17p (P-295-T-311) exerts pro-apoptotic actions in breast cancer cells in vitro and in vivo, independently from their ER alpha status

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TitleThe estrogen receptor alpha-derived peptide ER alpha 17p (P-295-T-311) exerts pro-apoptotic actions in breast cancer cells in vitro and in vivo, independently from their ER alpha status
Publication TypeJournal Article
Year of Publication2011
AuthorsPelekanou, V, Kampa M, Gallo D, Notas G, Troullinaki M, Duvillier H, Jacquot Y, Stathopoulos EN, Castanas E, Leclercq G
JournalMolecular Oncology
Volume5
Issue1
Pagination36-47
Date PublishedFeb
ISBN Number1574-7891
Accession NumberISI:000287617600004
Abstract

In recent years, our knowledge on estrogen receptors (ER) has been modified profoundly with the identification and the deciphering of the role of its protein effectors, as well as with the deeper insight of its molecular structure/function dynamics, characteristics associated with its nucleo-cytoplasmic-membrane shuttling properties. Also, significant progress has been made concerning its turn-over and associated final proteasomal degradation processes. These advances could lead in the near future to the design and the synthesis of novel receptor-interacting drugs. Recently, a number of receptor-related peptides acting as specific ER ligands have been identified and extensively studied with respect to their estrogenic/antiestrogenic activities. Among them, ER alpha 17p, a synthetic analog of the P-295-T-311 sequence of ER alpha, has been shown to exert pseudo-estrogenic effects by interacting in the close vicinity of its hinge region (BF3 domain). Remarkably, this sequence appears as the epicenter of a number of post-transcriptional modifications as well as of the recruitment of co-regulators, suggesting that it would play a key role in ERa functions. Here, we provide evidence that ERa17p induces apoptosis in ER alpha-positive (MCF-7, T47D) and -negative (MDA-MB-231, SK-BR-3) breast cancer cells by an ER alpha-independent membrane mechanism, triggering major proapoptotic signaling cascades. Finally, ER alpha 17p induces the regression of breast ER alpha-negative cancer tumor xenografts, without apparent toxicity, suggesting that it could represent a new attractive tool for the development of future promising therapeutic approaches, and providing a novel insight to ER regulation of cell fate. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

URL<Go to ISI>://000287617600004
DOI10.1016/j.molonc.2010.11.001
Short TitleThe estrogen receptor alpha-derived peptide ER alpha 17p (P-295-T-311) exerts pro-apoptotic actions in breast cancer cells in vitro and in vivo, independently from their ER alpha status
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