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Unraveling the Role of GPER in Breast Cancer

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Advances in Rapid Sex-Steroid Action

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Abstract

The G protein-coupled estrogen receptor-1 (GPER, formerly called GPR30) has been recently involved in the multifaceted transduction pathways through which estrogens induce diverse biological responses as well as pathological processes, including cancer development and progression. In this regard, it has been shown that not only estrogens but also antiestrogens binding to and activating the GPER-dependent signaling elicit stimulatory effects in hormone-dependent tumors like breast cancer. In accordance with these findings, GPER expression was associated with worse clinical features commonly used to assess the progression of breast malignancies, such as the detection of distant metastases. On the basis of diverse studies demonstrating the potential role of GPER in mediating the stimulatory action of estrogens in breast tumor, GPER may be considered as a valuable target toward novel therapeutic strategies against the development of breast cancer. Furthermore, the promiscuous activity exerted by antiestrogens, which act as GPER agonists and antagonists of the nuclear estrogen receptors, addresses the need of new selective estrogen receptor inhibitors.

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Abbreviations

AP-1:

activating protein-1

cAMP:

cyclic AMP

cDNA:

complementary DNA

EGFR:

Epidermal Growth Factor Receptor

ERK:

extracellular signal-regulated kinase

MAPK:

mitogen-activated protein kinase

NF-κB:

Nuclear Factor-κB

OHT:

4-hydroxytamoxifen

ROS:

Reactive Oxygen Species

Sp-1:

stimulating factor-1

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Acknowledgments

This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, project n. 8925/2009; http://www.airc.it/) and Ministero dell’Università e Ricerca Scientifica e Tecnologica (MIUR; http://www.istruzione.it/).

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Authors and Affiliations

  1. Department of Pharmaco-Biology, University of Calabria, Rende, CS, Italy

    Rosamaria Lappano & Marcello Maggiolini

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  1. Rosamaria Lappano
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  2. Marcello Maggiolini
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Correspondence to Marcello Maggiolini .

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Editors and Affiliations

  1. University of Naples, Naples, 80138, Italy

    Gabriella Castoria

  2. Department of Pathology, II University of Naples, Naples, 80138, Italy

    Antimo Migliaccio

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Lappano, R., Maggiolini, M. (2012). Unraveling the Role of GPER in Breast Cancer. In: Castoria, G., Migliaccio, A. (eds) Advances in Rapid Sex-Steroid Action. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1764-4_7

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