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17β-Estradiol enhances α5 integrin subunit gene expression through ERα–Sp1 interaction and reduces cell motility and invasion of ERα-positive breast cancer cells

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Abstract

In breast tumors the expression of estrogen receptor alpha (ERα) is known to be associated with a more favorable prognosis. ERα expression has been reported to reduce the metastatic potential of breast cancer cells. Recently, we have observed that extracellular matrix proteins activate ERα and that both liganded and unliganded receptor modulate cell invasiveness acting at nuclear level. To explain the mechanisms by which ERα regulates cell adhesion, we have evaluated the expression of α5β1 integrin, prevalently expressed in stationary cells, in response to 17β-estradiol (E2). Here we show that E2/ERα increases the expression of integrin α5β1 through Sp1-mediated binding to a GC-rich region located upstream of an ERE half-site in the 5′ flanking region of the α5 gene forming a ternary ERα–Sp1-DNA complex. Estrogen responsiveness of the α5 gene promoter, as observed in HeLa cells, underlies a general mechanism of regulation which is not strictly linked to the cell type. Our data reveal novel insight into the molecular mechanisms sustaining the reduced invasiveness of ERα expressing cells demonstrating that α5β1 integrin expression is related to the maintenance of the stationary status of the cells, counteracting E2/ERα capability to enhance breast cancer cell migration and invasion.

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Acknowledgments

Financial support: AIRC 2007, MIUR Ex 60%, and Regione Calabria.

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Authors and Affiliations

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

    Diego Sisci, Emilia Middea, Catia Morelli, Marilena Lanzino, Saveria Aquila, Stefania Catalano, Ivan Casaburi & Marcello Maggiolini

  2. Department of Cell Biology, University of Calabria, Arcavacata di Rende, Cosenza, 87030, Italy

    Pietro Rizza & Sebastiano Andò

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  1. Diego Sisci
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  2. Emilia Middea
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  3. Catia Morelli
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Correspondence to Sebastiano Andò.

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Diego Sisci and Emilia Middea contributed equally to this study.

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Sisci, D., Middea, E., Morelli, C. et al. 17β-Estradiol enhances α5 integrin subunit gene expression through ERα–Sp1 interaction and reduces cell motility and invasion of ERα-positive breast cancer cells. Breast Cancer Res Treat 124, 63–77 (2010). https://doi.org/10.1007/s10549-009-0713-6

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