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The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells

Maggiolini, Marcello
Vivacqua, Adele
Fasanella, Giovanna
Recchia, Anna Grazia
Sisci, Diego
Pezzi, Vincenzo
Montanaro, Daniela
Musti, Anna Maria
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Published in Journal of Biological Chemistry. 2004, vol. 279, no. 26, p. 27008-16
Abstract A growing body of evidence concerning estrogen effects cannot be explained by the classic model of hormone action, which involves the binding to estrogen receptors (ERs) alpha and ERbeta and the interaction of the steroid-receptor complex with specific DNA sequences associated with target genes. Using c-fos proto-oncogene expression as an early molecular sensor of estrogen action in ERalpha-positive MCF7 and ER-negative SKBR3 breast cancer cells, we have discovered that 17beta-estradiol (E2), and the two major phytoestrogens, genistein and quercetin, stimulate c-fos expression through ERalpha as well as through an ER-independent manner via the G protein-coupled receptor homologue GPR30. The c-fos response is repressed in GPR30-expressing SKBR3 cells transfected with an antisense oligonucleotide against GPR30 and reconstituted in GPR30-deficient MDA-MB 231 and BT-20 breast cancer cells transfected with a GPR30 expression vector. GPR30-dependent activation of ERK1/2 by E2 and phytoestrogens occurs via a Gbetagamma-associated pertussis toxin-sensitive pathway that requires both Src-related and EGF receptor tyrosine kinase activities. The ability of E2 and phytoestrogens to regulate the expression of growth-related genes such as c-fos even in the absence of ER has interesting implications for understanding breast cancer progression.
Keywords Breast Neoplasms/genetics/metabolismCell Line, TumorEstradiol/pharmacologyEstrogen Receptor alphaGenistein/pharmacologyHumansIsoflavones/pharmacologyMitogen-Activated Protein Kinase 1/metabolismMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinases/metabolismOligoribonucleotides, Antisense/pharmacologyPhosphorylationPhytoestrogensPlant Preparations/pharmacologyPlasmids/geneticsProto-Oncogene Proteins c-fos/antagonists & inhibitors/biosynthesis/geneticsQuercetin/pharmacologyRNA, Messenger/biosynthesisReceptors, Estrogen/metabolismReceptors, G-Protein-Coupled/genetics/physiologySignal TransductionTranscriptional Activation/drug effectsTransfectionUp-Regulation/drug effects
PMID: 15090535
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MAGGIOLINI, Marcello et al. The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. In: Journal of Biological Chemistry, 2004, vol. 279, n° 26, p. 27008-16. https://archive-ouverte.unige.ch/unige:4607

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Deposited on : 2009-12-04

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