title: GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.
abstract: BACKGROUND
  Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation.
  
  
  RESULTS
  We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation.
  
  
  CONCLUSIONS
  These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR U1065/UNS, Centre Méditerranéen de Médecine Moléculaire, Equipe 5 Environnement, Reproduction et Cancers Hormono-Dépendants, Nice, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chevalier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vega
authors.forename: Adil
authors.initials: A
authors.lastname: Bouskine
authors.forename: Bénazir
authors.initials: B
authors.lastname: Siddeek
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.forename: Daniel
authors.initials: D
authors.lastname: Chevallier
authors.forename: Patrick
authors.initials: P
authors.lastname: Fénichel
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000096:biosynthesis*; D018239:Seminoma / Q000378:metabolism* / Q000473:pathology; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000166:cytology
chemical_list: C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled