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Epidermal growth factor induces G protein-coupled receptor 30 expression in estrogen receptor-negative breast cancer cells

Albanito, Lidia
Sisci, Diego
Aquila, Saveria
Vivacqua, Adele
Madeo, Antonio
Lappano, Rosamaria
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Published in Endocrinology. 2008, vol. 149, no. 8, p. 3799-808
Abstract Different cellular receptors mediate the biological effects induced by estrogens. In addition to the classical nuclear estrogen receptors (ERs)-alpha and -beta, estrogen also signals through the seven-transmembrane G-protein-coupled receptor (GPR)-30. Using as a model system SkBr3 and BT20 breast cancer cells lacking the classical ER, the regulation of GPR30 expression by 17beta-estradiol, the selective GPR30 ligand G-1, IGF-I, and epidermal growth factor (EGF) was evaluated. Transient transfections with an expression plasmid encoding a short 5'-flanking sequence of the GPR30 gene revealed that an activator protein-1 site located within this region is required for the activating potential exhibited only by EGF. Accordingly, EGF up-regulated GPR30 protein levels, which accumulated predominantly in the intracellular compartment. The stimulatory role elicited by EGF on GPR30 expression was triggered through rapid ERK phosphorylation and c-fos induction, which was strongly recruited to the activator protein-1 site found in the short 5'-flanking sequence of the GPR30 gene. Of note, EGF activating the EGF receptor-MAPK transduction pathway stimulated a regulatory loop that subsequently engaged estrogen through GPR30 to boost the proliferation of SkBr3 and BT20 breast tumor cells. The up-regulation of GPR30 by ligand-activated EGF receptor-MAPK signaling provides new insight into the well-known estrogen and EGF cross talk, which, as largely reported, contributes to breast cancer progression. On the basis of our results, the action of EGF may include the up-regulation of GPR30 in facilitating a stimulatory role of estrogen, even in ER-negative breast tumor cells.
Keywords 5' Flanking Region/geneticsBase SequenceBinding SitesBreast Neoplasms/genetics/pathologyCell Proliferation/drug effectsCells, CulturedEpidermal Growth Factor/pharmacologyExtracellular Signal-Regulated MAP Kinases/physiologyGene Expression Regulation, Neoplastic/drug effectsHumansMolecular Sequence DataReceptor, Epidermal Growth Factor/physiologyReceptors, Estrogen/metabolismReceptors, G-Protein-Coupled/geneticsSignal Transduction/physiologyTranscription Factor AP-1/metabolismTransfectionUp-Regulation/drug effects
PMID: 18467441
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ALBANITO, Lidia et al. Epidermal growth factor induces G protein-coupled receptor 30 expression in estrogen receptor-negative breast cancer cells. In: Endocrinology, 2008, vol. 149, n° 8, p. 3799-808. doi: 10.1210/en.2008-0117 https://archive-ouverte.unige.ch/unige:4477

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Deposited on : 2009-12-01

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