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Oestrogens and selective oestrogen receptor (ER) modulators regulate EGF receptor gene expression through human ER α and β subtypes via an Sp1 site

Oncogene volume 22, pages 4875–4881 (2003)Cite this article

Abstract

Through the analysis of the transient expression of the luciferase reporter gene in HeLa cells, an evaluation has been made of the transcriptional activity of oestrogens and of selective oestrogen receptor (ER) modulators (SERMs), mediated by the α and β isoforms of the ER, on the epidermal growth factor receptor gene promoter. Oestrogen-activated ERβ presents a lower transcriptional activity compared with ERα, probably due to structural differences in the AF-1 regions of the receptors. Also SERMs induce different responses depending on the receptor isoform bound. Indeed, the phyto-oestrogens, genistein and daidzein, act as weak agonists of the oestrogenic activity via ERα, but as full agonists when bound to ERβ. The synthetic SERM 4OH-tamoxifen, on the other hand, displays an opposite behaviour since it exerts a full agonist action through ERα, but acts as a full antagonist via ERβ. As we have previously shown for ERα, an ERβ/Sp1 functional synergism has also been highlighted, by means of gel mobility shift assays. Moreover, our results show that the sensitivity of target tissues to oestrogens and SERMs can be affected by coexpression of ERs, depending on the formation of appropriate levels of homo- and heterodimers, thus providing a useful approach to predict the effects of hormonal treatment.

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Acknowledgements

This work was supported in part by grants from ADM, Decatur, Illinois, and in part by grants from CNR, Agenzia 2000 C008B98003.

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Authors and Affiliations

  1. National Research Council, Institute of Molecular Biology and Pathology, Rome, 00137, Italy

    Luisa Salvatori, Pierlorenzo Pallante, Linda Ravenna, Patrizia Chinzari & Elisa Petrangeli

  2. Department of Experimental Medicine and Pathology, University ‘La Sapienza’, Rome, 00161, Italy

    Luisa Salvatori, Patrizia Chinzari, Luigi Frati & Matteo A Russo

  3. Neuromed Institute, Pozzilli, 86077, Italy

    Luigi Frati

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  1. Luisa Salvatori
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Correspondence to Luisa Salvatori.

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Salvatori, L., Pallante, P., Ravenna, L. et al. Oestrogens and selective oestrogen receptor (ER) modulators regulate EGF receptor gene expression through human ER α and β subtypes via an Sp1 site. Oncogene 22, 4875–4881 (2003). https://doi.org/10.1038/sj.onc.1206784

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