title: Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF.
abstract: The steroid hormone oestrogen can signal through several receptors and pathways. Although the transcriptional responses mediated by the nuclear oestrogen receptors (ER) have been extensively characterized, the changes in gene expression elicited by signalling through the membrane-associated ER GPR30 have not been studied. We show here for ER-negative human breast cancer cells that the activation of GPR30 signalling by oestrogen or by hydroxytamoxifen (OHT), an ER antagonist but GPR30 agonist, induces a transcription factor network, which resembles that induced by serum in fibroblasts. The most strongly induced gene, CTGF, appears to be a target of these transcription factors. We found that the secreted factor connective tissue growth factor (CTGF) not only contributes to promote proliferation but also mediates the GPR30-induced stimulation of cell migration. These results provide a framework for understanding the physiological and pathological functions of GPR30. As the activation of GPR30 by OHT also induces CTGF in fibroblasts from breast tumour biopsies, these pathways may be involved in promoting aggressive behaviour of breast tumours in response to endogenous oestrogens or to OHT being used for endocrine therapy.
authors.affiliation: Département de Biologie Cellulaire, Sciences III, Université de Genève, Genève, Switzerland.
authors.forename: Deo Prakash
authors.initials: DP
authors.lastname: Pandey
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Lappano
authors.forename: Lidia
authors.initials: L
authors.lastname: Albanito
authors.forename: Antonio
authors.initials: A
authors.lastname: Madeo
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D055513:Connective Tissue Growth Factor / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004967:Estrogens; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D013629:Tamoxifen; D055513:Connective Tissue Growth Factor; C016601:afimoxifene